Donnie Darko and Chaperonin: Difference between pages

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[[Image:Chaperonin.PNG|thumb|A chaperonin called GroEL-GroES complex (from Escherichia coli) (PDB code=1aon). Two rings of 7x2GroEL proteins (shown in blue and green) with a cap (just on one side) of GroES proteins (red and yellow). Unfolded proteins enter that cavity (which is protein sized) to be protected during folding.
{{otheruses4|the 2001 film|the book|The Donnie Darko Book}}
([http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb32_1.html more details...])]]


A proportion of all newly-made proteins require assistance to convert from a linear chain of amino acids to a functional three-dimensional entity. This process is called [[protein folding]]. '''Chaperonins''' are protein complexes that assist the folding of these nascent, non-native polypeptides into their native, functional state. These proteins belong to a large class of molecules that assist protein folding, called [[molecular chaperone]]s.
{{Infobox Film
| name = Donnie Darko
| image = 6990 poster.jpg
| caption = Theatrical poster
| director = [[Richard Kelly (director)|Richard Kelly]]
| producer = [[Adam Fields]]<br />[[Nancy Juvonen]]<br />[[Sean McKittrick]]
| writer = [[Richard Kelly (director)|Richard Kelly]]
| narrator =
| starring = [[Jake Gyllenhaal]]<br />[[Jena Malone]]<br>[[James Duval]]<br />[[Maggie Gyllenhaal]]<br />[[Mary McDonnell]]<br>[[Holmes Osborne]]<br>[[Katharine Ross]]<br />with [[Drew Barrymore]]<br>[[Noah Wyle]]<br>and [[Patrick Swayze]]
| music = [[Michael Andrews (musician)|Michael Andrews]]
| cinematography = [[Steven B. Poster]]
| editing = [[Sam Bauer]]<br />[[Eric Strand]]
| distributor = [[Newmarket Films]]
| released = [[October 26]], [[2001]] ([[United States|USA]])
| runtime = 113 min. <small>(original cut)</small><br />133 min. <small>(director's cut)</small>
| country = [[USA]] [[Image:Flag of the United States.svg|22px]]
| language = [[English language|English]]
| budget = [[United States dollar|US$]]4.5 million
| gross = US$4,116,307 <small>(worldwide)</small>
| preceded_by =
| followed_by = ''[[S. Darko]]''
| amg_id = 1:237115
| imdb_id = 0246578
}}
'''''Donnie Darko''''' is a [[2001 in film|2001]] [[Cult film|cult classic]] [[psychological thriller]] [[film]] written and directed by [[Richard Kelly (director)|Richard Kelly]], and starring [[Jake Gyllenhaal]], [[Jena Malone]], and [[Maggie Gyllenhaal]]. The film depicts the reality-bending venture of the eponymous character as he seeks the meaning and significance of his troubling [[Doomsday event|end-of-the-world]] visions.


These molecular machines use chemical energy, in the form of [[Adenosine triphosphate]] (ATP), to promote protein folding in all cells.
The film initially was slated for a [[direct-to-video]] release before it was picked up by [[Newmarket Films]]. Budgeted with $4,500,000 and filmed over the course of 28 days, the movie just missed breaking even, grossing about $4,200,000 worldwide. The film has since gone on to receive favorable reviews from critics and a cult following among fans.<ref name="rotten1">{{Cite web|url=http://www.rottentomatoes.com/m/donnie_darko/|title=''Donnie Darko'' film review|accessdate=2008-09-11|publisher=IGN.com|year=2001|work=Rotten Tomatoes}}</ref> A sequel to the film, entitled ''[[S. Darko]]'', is expected to be released in 2009.


== Plot ==
==Structure==
The structure of these chaperonins resemble two donuts stacked on top of one another to create a barrel.
Donnie Darko (played by [[Jake Gyllenhaal]]) is a troubled teenager in suburban [[Virginia]] in 1988. He appears to be suffering the symptoms of [[schizophrenia|paranoid schizophrenia]]. At the start of the film, he has recently stopped taking his medication and as a result is [[sleepwalking]]. His parents, Rose and Eddie ([[Mary McDonnell]] and [[Holmes Osborne]]) and his sisters, Elizabeth and Samantha ([[Maggie Gyllenhaal]] and [[Daveigh Chase]]), are concerned about him. One night at dinner, Donnie and his sister get into a profane argument during which Elizabeth reveals she knows Donnie is no longer taking his medication. Rose confronts Donnie in his bedroom and he calls her a "bitch". Guiltily, Donnie resumes taking his medication. On [[October 2]], however, he sleepwalks and meets Frank ([[James Duval]]), a man in a menacing [[rabbit|bunny]] costume. Frank tells him that in 28 days, 6 hours, 42 minutes and 12 seconds, the world will end. That night, a jet engine mysteriously crashes through the roof of the Darkos' house, destroying Donnie's room.


Each ring is composed of either 7, 8 or 9 subunits depending on the organism in which the chaperonin is found.
As Eddie drives Donnie to the office of Dr. Thurman ([[Katharine Ross]]), Donnie's therapist, Eddie nearly runs over Roberta Sparrow, also known as "Grandma Death" ([[Patience Cleveland]]). A [[senile]] old woman who spends her days walking back and forth from her house to the [[mailbox]] across the street, Grandma Death whispers in Donnie's ear that all living creatures on Earth ultimately die alone. This greatly troubles Donnie, who worries that life has no meaning.


== Categories of Chaperonins ==
A few days later, Frank appears to Donnie in a [[hallucination]] and urges him to flood the private school he attends by breaking open the water main with an axe. Donnie also embeds the axe in the head of the school's solid bronze statue of its mascot and spray-paints "They made me do it" on the sidewalk. School is canceled that day and Donnie walks home Gretchen ([[Jena Malone]]), the new girl in school. She reveals that her stepfather nearly killed her mother and is still on the loose. Donnie reveals his own troubled past as well as his intelligence. Gretchen decides that Donnie is weird and that this makes him attractive. They agree to become a couple.
===Group I===
Group I chaperonins are found in [[prokaryotes]] as well as [[organelles]] of [[endosymbiotic]] origin: [[chloroplasts]] and [[mitochondria]].


The GroEL/GroES complex in ''[[E. coli]]'' is a Group I chaperonin and the best characterized large (~ 1 MDa) chaperonin complex.
Donnie has a troubled relationship with the faculty at his [[high school]]. Ms. Pomeroy ([[Drew Barrymore]]) appreciates his intellect and ability to engage with and understand the difficult material she assigns them to read in English class. The science teacher, Dr. Monnitoff ([[Noah Wyle]]), finds him a little more troubling, and Kitty Farmer ([[Beth Grant]]), the highly strung and [[socially conservative]] health instructor, is offended that he questions her use of self-help tapes in class. After he profanely rejects her use of the simplistic methods espoused by local celebrity Jim Cunningham ([[Patrick Swayze]]), Donnie finds himself suspended from after-school activities. When Donnie verbally assaults Cunningham during an appearance at the high school, he gets in even deeper trouble. Although the administration suspects that Donnie is indeed responsible for the vandalism, he is never charged.
* [[GroEL]] is a double-ring 14mer with a greasy [[hydrophobic]] patch at its opening; it is so large it can accommodate native folding of 54-kDa [[Green fluorescent protein|GFP]] in its central cavity.
* [[GroES]] is a single-ring heptamer that binds to GroEL in the presence of ATP or transition state analogues of ATP hydrolysis, such as ADP-AlF<sub>3</sub>. It's like a cover that covers GroEL (box/bottel).
GroEL/GroES may not be able to undo protein aggregates, but kinetically it competes in the pathway of misfolding and aggregation, thereby preventing aggregate formation.<ref name="pmid14686103">{{cite journal | author = Fenton WA, Horwich AL | title = Chaperonin-mediated protein folding: fate of substrate polypeptide | journal = Q. Rev. Biophys. | volume = 36 | issue = 2 | pages = 229–56 | year = 2003 | month = May | pmid = 14686103 | doi = 10.1017/S0033583503003883| url = | issn = }}</ref>


===Group II===
Frank continues to appear to Donnie and tells Donnie that they can do anything and won't get caught. Frank also tells Donnie about [[time travel]], further confusing him. Soon, Donnie sees tubes of fluid light extending out of his family's chests, indicating where they will go. His own tube beckons him to follow as it enters his parents' room and reveals the gun his father keeps in a box in the closet. Donnie speaks about time travel with Dr. Monnitoff who gives him a book, "The Philosophy of Time Travel," written by Roberta Sparrow. She used to be a nun and a teacher at the high school. However, the climate at the school is becoming increasingly conservative as Kitty Farmer leads a protest against Ms. Pomeroy's choice of reading material; one of the stories she had assigned, [[Graham Greene]]'s "[[The Destructors]]," features teenagers who flood a man's house by breaking a water pipe. Ms. Pomeroy is fired and Dr. Monnittoff, who is also her boyfriend, refuses to discuss time travel with Donnie once his questions take a theological direction.
Group II chaperonins, found in the [[eukaryotic]] [[cytosol]] and in [[archaebacteria]], are more poorly characterized.


TRiC (TCP-1 Ring Complex, also called CCT), the eukaryotic chaperonin, is composed of eight different though related subunits, each thought to be represented once per eight-membered ring. TRiC was originally thought to fold only the cytoskeletal proteins actin and tubulin but is now known to fold dozens of substrates.
Gretchen and Donnie grow closer. She is one of the few people he opens up to about his time travel visions, and they discuss how they wish they could travel back in time and prevent the bad things in their lives from happening. Dr. Thurman increases Donnie's medication and begins [[hypnotherapy]] with him. But Frank continues to appear to Donnie. One night, Donnie and Gretchen go to see a [[horror movie]]. Gretchen falls asleep and Frank appears. When Donnie asks Frank why he wears a "stupid bunny suit," Frank asks Donnie why he wears a "stupid man suit," then acquiesces and takes the head off, revealing a young adult with a gruesome wound in his right eye. When Donnie asks about the cause of the eye wound, Frank whispers "I am so sorry" and then directs Donnie's attention to the movie screen. A portal opens, revealing Jim Cunningham's house. Frank tells Donnie to burn it to the ground. Donnie leaves the sleeping Gretchen in the theatre and does as Frank tells him to. He is not caught, and [[firefighters]] discover a dungeon of [[child pornography]] in a hidden room in the mansion. Cunningham is arrested the next morning. Kitty Farmer, a friend and devoted follower of Cunningham's, decides she must lead his public defense and asks Rose to accompany the school's dance team, Sparkle Motion, to Los Angeles to appear on [[Star Search]]. Samantha is Sparkle Motion's lead dancer and, against her better judgment, Rose agrees. Eddie is away on business, so this means Elizabeth and Donnie are on their own.


Mm cpn (Methanococcus maripaludis chaperonin), found in the archaea Methanococcus maripaludis, is composed of sixteen identical subunits (eight per ring). It has been shown to fold the mitochondrial protein rhodanese; however, no natural substrates have yet been identified.
Elizabeth is accepted into [[Harvard]], and she and Donnie decide to throw a [[Halloween]] [[party]] to celebrate. The night of the party ([[October 30]]), Gretchen comes to Donnie's house for safety because her mother has suddenly disappeared. Donnie comforts her and they presumably make love, ignoring phone calls from Donnie's desperate therapist (who knows that Donnie is responsible for the vandalism to the high school and Jim Cunningham's house) and Rose, who calls to announce that Sparkle Motion won their initial Star Search competition and that they will return on a [[red eye flight]] that night.


Group II chaperonins are not thought to utilize a GroES-type cofactor to fold their substrates. They instead contain a "built-in" lid that closes in an ATP-dependent manner to encapsulate its substrates, a process that is required for optimal protein folding activity.
At midnight, Donnie has another [[hallucination]] about the fluid light tunnels. He realizes that the 28 days have passed, and that only 6 hours remain until the end of the world. Convinced that Grandma Death is in some way connected to Frank, Donnie persuades Gretchen and two other friends to go with him to her house. When they get there, they are assaulted by the high school's resident bullies ([[Alex Greenwald]] and [[Seth Rogen]]). Gretchen is thrown dazed into the road, where she is struck and killed by a car driven by Frank ([[James Duval]]), Elizabeth's boyfriend who is on his way to their Halloween party. Frank is wearing the creepy bunny costume that Donnie's hallucination wears. Donnie uses his father's [[gun]] to shoot Frank in the right eye, killing him, then carries Gretchen's body to his home. He steals the car keys from a sleeping Elizabeth and, taking Gretchen with him, drives into the hills above town.


== Mechanism of action ==
From that vantage point, Donnie can see a time tunnel forming over the town. The red eye flight carrying Rose and Sparkle Motion enters the turbulence created by the time tunnel, and one of the engines on the jet breaks free and falls into the tunnel. Donnie looks at Gretchen with love and the primary universe is reset to October 2nd.
Chaperonins undergo large conformational changes during a folding reaction as a function of the enzymatic [[hydrolysis]] of ATP as well as binding of substrate proteins and cochaperonins, such as GroES. These conformational changes allow the chaperonin to bind an unfolded or misfolded protein, encapsulate that protein within one of the cavities formed by the two rings, and release the protein back into solution. Upon release, the substrate protein will either be folded or will require further rounds of folding, in which case it can again be bound by a chaperonin.


== Conservation of structural and functional homology ==
It is back to [[October 2]]. Donnie is in bed, creating [[predestination paradox]]. On this occasion, he chooses to stay in bed (presumably to save the girlfriend he will never meet). Shortly after he goes to sleep, the jet engine from the red eye flight on October 30 crashes through the roof, killing him (In a deleted scene director's cut DVD it is revealed that he was actually impaled by a piece of wood from the broken roof). As Donnie's body is taken away, all the people affected by Donnie's actions are stunned: Frank, Elizabeth's boyfriend subconsciously touches his right eye and everyone else is suddenly sad. Gretchen, having never met Donnie, rides by on her bicycle. She learns from a neighbor what has happened and waves to Rose, who is smoking a cigarette (the last encounter she had with Donnie was the unpleasant argument). There is an air of mutual recognition between them.
As mentioned, all cells contain chaperonins.
* In bacteria, the archetype is the well-characterized chaperonin [[GroEL]] from E. coli.
* In [[archaea]], the chaperonin is called the [[thermosome]].
* In [[eukarya]], the chaperonin is called CCT (also called [[TRiC]] or c-cpn).


These protein complexes appear to be essential for life in ''[[E. coli]]'', ''[[Saccharomyces cerevisiae]]'' and higher [[eukaryotes]]. While there are differences between eukaryotic, bacterial and archaeal chaperonins the general structure and mechanism are conserved.
== Director's interpretation ==
Writer/director [[Richard Kelly (director)|Richard Kelly]] does not deny the validity of personal interpretations, but has expressed his own theories through the extra commentary on the two DVDs, his own (fictional) book ''The Philosophy of Time Travel'', and in various other interviews.


== References ==
According to Kelly and his ''Philosophy of Time Travel'', at midnight on [[October 2]] a ''[[Tangent]] [[Universe]]'' branches off the Primary Universe around the time when Donnie is called out of his bedroom by Frank, immediately before the appearance of the Artifact, the faulty [[jet engine]]. The inherently unstable Tangent Universe will collapse in just over 28 days and take the ''Primary Universe'' with it if not corrected. Closing the Tangent Universe is the duty of the ''Living Receiver'', Donnie, who wields certain supernatural powers to help him in the task.
<references/>


== See also ==
Those who die within the Tangent Universe (and would not have died otherwise) are the ''Manipulated Dead'' (Frank, Gretchen). Manipulated Dead Frank, at least, is also given certain powers in that he is able to subtly understand what is happening and have the ability to contact and influence the ''Living Receiver'' via the ''Fourth Dimensional Construct'' (water). All others within the orbit of the Living Receiver are the ''Manipulated Living'' (e.g. Ms. Pomeroy, Dr. Monnitoff), subconsciously drawn to push him towards his destiny to close the Tangent Universe and, according to the ''Philosophy of Time Travel'', die by the Artifact.
* [[Chaperone (protein)|Chaperone]]

* [[Heat shock protein]]
Frank appears in the story in two guises (indeed, three guises if we assume that he 'never' dies on account of the restoration of the Primary Universe through the negation of the Tangent Universe). Firstly, there is the Manipulated Dead Frank who appears to Donnie as a premonition from the future of the Tangent Universe in the disturbing rabbit suit. Dead Frank is aware of Donnie's fate and destiny, and impels him to realize it so that the Primary Universe can be restored at the point where/when the Tangent Universe branched off from it. Secondly, there is the living boyfriend of Donnie's sister, Elizabeth, whose fate unfolds within the Tangent Universe by means of Donnie's successes in realizing his mission. This living boyfriend is fatally (in both senses) shot by Donnie towards the end of the film, a killing which was foreseen by Donnie (albeit through a glass darkly).

With regards to Donnie's mission, the question arises as to whether his success in fulfilling it was predetermined. If we assume that it was, then Donnie was fated to die a young death in the Primary Universe. If we assume that it was not, then there would not have necessarily been a Manipulated Dead Frank to guide Donnie on his mission. The fact that such a Frank existed suggests that it is probably the case that Donnie was, throughout the film, taking the inevitable steps towards his own annihilation.

==Cast==
*[[Jake Gyllenhaal]] as Donald J. "Donnie" Darko
*[[Jena Malone]] as Gretchen Ross
*[[James Duval]] as Frank
*[[Maggie Gyllenhaal]] as Elizabeth Darko
*[[Mary McDonnell]] as Rose Darko
*[[Holmes Osborne]] as Eddie Darko
*[[Katharine Ross]] as Dr. Lilian Thurman
*[[Drew Barrymore]] as Karen Pomeroy
*[[Noah Wyle]] as Dr. Kenneth Monnitoff
*[[Patrick Swayze]] as Jim Cunningham
*[[Daveigh Chase]] as Samantha "Sam" Darko
*[[Beth Grant]] as Kitty Farmer
*[[Stuart Stone]] as Ronald Fisher
*[[Alex Greenwald]] as Seth Devlin
*[[Seth Rogen]] as Ricky Danforth
*[[Patience Cleveland]] as Roberta Sparrow ("Grandma Death")
*[[Jolene Purdy]] as Cherita Chen
*[[Ashley Tisdale]] as Kim
*[[Jerry Trainor]] as Lanky Kid
*[[Cliffy Tucker]] as Reggie Johnson

== Production ==
=== Filming ===
<!-- Commented out because image was deleted: [[Image:Donnie-darko-8.jpg|thumb|right|250px|The "Carpathian ridge" scenes were shot on the Angeles Crest Highway.<ref>{{cite video
| people =Poster, Steven (Cinematographer)
| title =Donnie Darko Production Diary
| medium =DVD
| publisher = [[20th Century Fox]]
| date =2004}}</ref>]] -->
''Donnie Darko'' was filmed in 28 days on a budget of [[United States dollar|US$]]4.5 million.<ref>{{cite web | url = http://richard-kelly.net/darko/index.html | title = Donnie Darko | publisher = Richard-Kelly.net (unofficial fansite) | accessdate = 2007-03-05}}</ref>
It almost went straight to home video release but was publicly released by the production company [[Flower Films]].<ref>{{cite news | title = 'Darko' takes a long, strange trip | accessdate = 2005-02-14 | url = http://www.usatoday.com/life/movies/news/2005-02-14-dvd-donnie-darko_x.htm | publisher = [[USA Today]]}}</ref>

The film was shot in [[California]]. [[Loyola High School (Los Angeles)|Loyola High School]], a prominent [[Catholic]] school in [[Los Angeles, California]], was used as Donnie's [[high school]]. The house where the Darko family lives is located in [[Long Beach, California]]. Donnie awakens in a [[golf course]] in [[Long Beach, California]]; the hotel where his family lodges is the Burbank, California, [[Holiday Inn]]; and the Aero theater where Donnie and Gretchen watch the double feature is a cinema in [[Santa Monica, California]].

=== Music ===
{{Main|Donnie Darko (soundtrack)}}
In 2003, composer [[Michael Andrews (musician)|Michael Andrews]] and singer [[Gary Jules]] found their piano-driven cover of the [[Tears for Fears]]' hit "[[Mad World]]", featured in the film as part of the end sequence, and was the UK Christmas Number One single in 2003.<ref>{{cite web| url=http://www.indiewire.com/movies/movies_040722darko.html| title = Donnie Darko| publisher = Indie Wire| accessdate = 2006-05-17}}</ref>

A slightly remixed part of the song was used in the [[David Fincher]] directed TV commercial for the 2006 [[Xbox 360]] [[Video game|game]] ''[[Gears of War]]''. The advertisement brought the song an increased level of popularity, propelling it to [http://www.joystiq.com/2006/11/27/mad-world-gears-ad-propels-song-to-1-on-itunes/ number one] in downloads at the [[iTunes]] music store in late 2006. This song has also had a strong presence in Internet culture, as it has been used countless times for fan videos and trailers. The song was also used at the end of an episode of ''[[CSI: Crime Scene Investigation|CSI]]'', at the end of an episode of ''[[Jericho tv|Jericho]]'', in ''[[Smallville (TV series)|Smallville]]'', and the end of an episode of ''[[The Cleaner (TV series)|The Cleaner]]''.

Other mainstream songs appear in the film, all of which are featured on the first CD of the British edition of the soundtrack. One continuous sequence involving an introduction of Donnie's high school prominently features the song "[[Head Over Heels (Tears for Fears song)|Head Over Heels]]" by [[Tears for Fears]], Samantha's dance group, "Sparkle Motion," performs with the song "[[Notorious (song)|Notorious]]" by [[Duran Duran]], and "[[Under the Milky Way]]" by [[The Church (band)|The Church]] is played after Donnie and Gretchen emerge from his room during the party. "[[Love Will Tear Us Apart]]" by [[Joy Division]] also appears in the film during the party and shots of Donnie and Gretchen upstairs. However, the version included was released in 1995, although the film is set in 1988. The opening sequence is set to "[[The Killing Moon]]" by [[Echo & The Bunnymen]], which relates to the plot of the film on two levels. First, Donnie's plight, newly found views on time travel and eventual demise are reflected in the chorus lines "''Fate up against your will[...] will wait until you give yourself to him''". Second, these lines delivered by "The Bunnymen" foreshadow the appearance of Frank as an agent of Fate.

== Release ==
The limited release of this film happened only a week before the [[9-11 attacks]]. It was then held back for almost a year on the international releases, where it fared much better and was viewed by many more cinema goers. From here the cult following of this movie began, and the DVD release of the film brought it again to American audiences.

=== Marketing ===
*''[[The Donnie Darko Book]]'' (2003), written by Richard Kelly and introduced by Jake Gyllenhaal, explains some of the film's details. The script is the director's cut.
*[[National Entertainment Collectibles Association|NECA]] released first a six-inch (15&nbsp;cm) figure of Frank the Bunny and later a foot-tall (30&nbsp;cm) 'talking' version of the same figure.

=== Home video ===
The film was originally released on DVD and VHS in March 2002. Strong DVD sales led [[Newmarket Films]] to release a "[[Director's cut|Director's Cut]]" on DVD in 2005. [[Bob Berney]], President of Newmarket Films, described the film as "a runaway hit on DVD," citing US sales of more than $10 million.

The director's cut of the film was released on [[May 29]], [[2004]], in [[Seattle, Washington]], at the [[Seattle International Film Festival]] and later in [[New York City]] and [[Los Angeles]] on [[July 23]], [[2004]]. This cut includes twenty minutes of extra footage, an altered soundtrack, the director's interpretation, and visual excerpts from the book ''The Philosophy of Time Travel''. The director's cut DVD, released on [[February 15]], [[2005]], included the new [[footage]] and more soundtrack changes, as well as some additional features exclusive to the two-DVD set: excerpts from the storyboard, a 52-minute production diary, "#1 fan video," a "cult following" video interviewing British fans, and the new director's cut cinematic trailer. The director's cut DVD was released as a giveaway with copies of the British ''Sunday Times'' newspaper on [[February 19]] [[2006]].

== Reception ==
=== Box office performance ===
The film debuted in U.S. theaters in October 2001 to a tepid response. Shown on only 58 screens nationwide, the film grossed $110,494 in its opening weekend. By the time the film closed in U.S. theaters on [[April 11]], [[2002]], it had grossed $517,375.<ref>{{cite web| url=http://www.boxofficemojo.com/movies/?page=releases&id=donniedarko.htm| title = Donnie Darko| publisher = Box Office Mojo| accessdate = 2006-05-17}}</ref><ref>{{cite web| url=http://imdb.com/title/tt0246578/business| title = Donnie Darko| publisher = IMDB| accessdate = 2006-05-17}}</ref>

Despite the poor showing at the box office, the film had attracted a devoted fan base. It was originally released on DVD and VHS in March 2002. During this time, the Pioneer Theatre in New York City's East Village began midnight screenings of ''Donnie Darko'' that continued for 28 consecutive months.<ref>{{cite web| url=http://www.indiewire.com/movies/movies_040722darko.html| title = Donnie Darko| publisher = Indie Wire| accessdate = 2006-05-17}}</ref>

=== Critical reception ===
''Donnie Darko'' had its first screening at the [[Sundance Film Festival]] on January 19, 2001. Critic [[Andy Bailey]] billed ''Donnie Darko'' as a "Sundance surprise" that "isn't spoiled by the Hollywood forces that helped birth it."
Receiving plenty of critical acclaim, Rotten Tomatoes gave the film an 83% rating, while Metacritic gave it a 71% rating. Jean Oppenheimer of ''New Times (LA)'' praised the film, saying, "Like gathering storm clouds, Donnie Darko creates an atmosphere of eerie calm and mounting menace -- stands as one of the most exceptional movies of 2001." <ref>{{cite web| url=http://www.indiewire.com/movies/rev_01Sund_010121_Darco.html| title = Donnie Darko| publisher = Indie Wire| accessdate = 2006-05-17}}</ref>

=== Awards ===
2001 &mdash; [[Richard Kelly (director)|Richard Kelly]] won with ''Donnie Darko'' for "Best Screenplay" at the [[Catalonian]] International Film Festival and at the [[San Diego]] Film Critics Society. Donnie Darko also won the "Audience Award" for Best Feature at the [[Sweden]] Fantastic Film Festival. The film was nominated for "Best Film" at the Catalonian International Film Festival and for the "Grand Jury Prize" at the [[Sundance Film Festival]].

2002 &mdash; Donnie Darko won the "Special Award" at the Young Filmmakers Showcase at the Academy of Science Fiction, Fantasy and Horror Films. The movie also won the "Silver Scream Award" at the [[Amsterdam]] Fantastic Film Festival. Kelly was nominated for "Best First Feature" and "Best First Screenplay" with ''Donnie Darko'', as well as Jake Gyllenhaal being nominated for "Best Male Lead," at the Independent Spirit Awards. The film was also nominated for the "Best Breakthrough Film" at the Online Film Critics Society Awards.

2003 &mdash; Jake Gyllenhaal won "Best Actor" and Richard Kelly "Best Original Screenplay" for ''Donnie Darko'' at the Chlotrudis Awards, where Kelly was also nominated for "Best Director" and "Best Movie."

2005 &mdash; ''Donnie Darko'' ranked in the top five on [[My Favourite Film]], an [[Australia]]n poll conducted by the [[Australian Broadcasting Corporation|ABC]].<ref>{{cite web| url=http://www.abc.net.au/myfavouritefilm/| title = My Favourite Film| publisher = ABC| accessdate = 2006-07-11}}</ref>

2006 &mdash; ''Donnie Darko'' ranks ninth in FilmFour's [[50 Films to See Before You Die]].<ref>{{cite web| url=http://www.brandrepublic.com/bulletins/br/article/567497/c4-relaunches-film4-50-films-die-countdown/
| title = C4 relaunches Film4 with '50 films to see before you die' list countdown| publisher = Brand Republic| accessdate = 2006-09-16}}</ref>

2008 &mdash; ''Donnie Darko'' ranks #125 on [[IMDB]].<ref>{{cite web| url=http://imdb.com/
| title = IMDB| publisher = Brand Republic| accessdate = 2006-09-16}}</ref>
's Top 250 Films.

It also came in at number 14 on [[Entertainment Weekly]]'s list of the [http://www.ew.com/ew/gallery/0,,1532588,00.html 50 Best High School Movies] and landed at number 2 in their "[[Greatest Independent Films of All Time]]" list.

== Adaptations ==
[[Marcus Stern]], Associate Director of the [[American Repertory Theatre]], directed a staged adaptation of ''Donnie Darko'' at the Zero Arrow Theatre in [[Cambridge, Massachusetts|Cambridge]], [[Massachusetts]], in the fall of 2007. It ran from [[October 27]] to [[November 18]], [[2007]], with opening night fittingly scheduled on Halloween.
An article written by the production dramaturg stated that the director and production team planned to "embrace the challenge to make the fantastical elements come alive on stage."<ref>{{cite web
| url = http://www.amrep.org/articles/6_1c/bringing.html
| title = Bringing the End of the World to Life
| author = Sarah Wallace
| publisher = [[American Repertory Theatre]]
| date = [[2007-08-07]]
| accessdate = 2007-10-14
}}</ref> More details and commentary about the production can be found on the [http://www.amrep.org/darko A.R.T.'s official website] and [http://amrep.wordpress.com/category/0708-season/donnie-darko A.R.T.'s official blog]. In 2004, Stern adapted and directed Kelly's screenplay for a graduate student production at the American Repertory Theatre's [[Institute for Advanced Theatre Training]] (I.A.T.T./M.X.A.T.).

==Sequel==
{{Main|S. Darko}}
On [[May 18]], [[2008]], filming began for ''S. Darko'', the sequel to ''Donnie Darko''. [[UK]]-based sales company Velvet Octopus will be launching sales for the film in [[2008 Cannes Film Festival|Cannes]], with [[20th Century Fox|Fox]] already having acquired [[North American]] rights. ''S. Darko'' will be set seven years after the end of ''Donnie Darko''; Donnie's little sister Samantha and her best friend Corey are now 17 and on a [[roadtrip]] to [[Los Angeles, California|Los Angeles]] when they are plagued by bizarre visions. [[Daveigh Chase]], who portrayed Samantha Darko in ''Donnie Darko'', will be reprising her role. The [[cast]] will also include [[Ed Westwick]], [[Briana Evigan]], and [[Justin Chatwin]]. [[Chris Fisher]] will direct the film, shooting on an estimated $10,000,000 budget and commenting he is "a great admirer of [[Richard Kelly (director)|Richard Kelly]]'s film and hope[s] to create a similar world of blurred fantasy and reality." ''Donnie Darko'' director Kelly is, however, not involved - he claimed in the director's cut commentary that he would never make a sequel, because he wanted to maintain the integrity of the film and just put the film to rest. According to Simon Crowe of Velvet Octopus, the [[Fictional character|character]] Donnie will not be coming back, but there will be "meteorites and rabbits".<ref>{{cite web
| url = http://www.screendaily.com/ScreenDailyArticle.aspx?intStoryID=38664&Category=
| title = Donnie Darko sequel S. Darko starts shooting May 18
| author = Wendy Mitchell
| publisher = [[Screen Daily]]
| date = [[2008-05-09]]
| accessdate = 2008-05-09
}}</ref>

== References ==
{{Reflist|2}}
*{{Citation
| last1 = Commentary with Kevin Smith
| title = Donnie Darko Directors Cut
| publisher = Faber and Faber
| year = 2003
| isbn = 0571221246
}}.


== External links ==
==External links==
* {{MeshName|Chaperonins}}
{{Wikiquote}}
*[http://www.donniedarkofilm.com DonnieDarkoFilm.com] - Official website
*{{Imdb title|id=0246578|title=Donnie Darko}}
*{{Rotten-tomatoes|id=donnie_darko|title=Donnie Darko}}
*{{Rotten-tomatoes|id=donnie_darko_directors_cut|title=Donnie Darko: The Director's Cut}}
*[http://www.stainlesssteelrat.net/ddfaq.htm The Donnie Darko FAQ]
*[http://www.locusmag.com/2003/Reviews/Person04_Darko.html Extensive analysis of the film by [[Lawrence Person]]]
*[http://www.ruinedeye.com/cd/index.htm Cellar Door: with web site guide]
*[http://www.donniedarko.info Donnie Darko Facts]


{{Chaperones}}
{{Richard Kelly Films}}


[[Category:2001 films]]
[[Category:Proteins]]
[[Category:American films]]
[[Category:Cell biology]]
[[Category:Art films]]
[[Category:WikiProject Molecular and Cellular Biology articles]]
[[Category:Avant-garde and experimental films]]
[[Category:Coming-of-age films]]
[[Category:Directorial debut films]]
[[Category:Donnie Darko]]
[[Category:Drama films]]
[[Category:English-language films]]
[[Category:Existentialist works]]
[[Category:Films set in the 1980s]]
[[Category:Films set in Virginia]]
[[Category:Neo-noir]]
[[Category:Philosophical films]]
[[Category:Psychological science fiction films]]
[[Category:Satirical films]]
[[Category:Teen films]]
[[Category:Time travel films]]
[[Category:Tragedy films]]
[[Category:Wormholes in fiction]]
[[Category:Films directed by Richard Kelly]]
[[Category:Plays based on media]]


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Revision as of 10:25, 11 October 2008

File:Chaperonin.PNG
A chaperonin called GroEL-GroES complex (from Escherichia coli) (PDB code=1aon). Two rings of 7x2GroEL proteins (shown in blue and green) with a cap (just on one side) of GroES proteins (red and yellow). Unfolded proteins enter that cavity (which is protein sized) to be protected during folding. (more details...)

A proportion of all newly-made proteins require assistance to convert from a linear chain of amino acids to a functional three-dimensional entity. This process is called protein folding. Chaperonins are protein complexes that assist the folding of these nascent, non-native polypeptides into their native, functional state. These proteins belong to a large class of molecules that assist protein folding, called molecular chaperones.

These molecular machines use chemical energy, in the form of Adenosine triphosphate (ATP), to promote protein folding in all cells.

Structure

The structure of these chaperonins resemble two donuts stacked on top of one another to create a barrel.

Each ring is composed of either 7, 8 or 9 subunits depending on the organism in which the chaperonin is found.

Categories of Chaperonins

Group I

Group I chaperonins are found in prokaryotes as well as organelles of endosymbiotic origin: chloroplasts and mitochondria.

The GroEL/GroES complex in E. coli is a Group I chaperonin and the best characterized large (~ 1 MDa) chaperonin complex.

  • GroEL is a double-ring 14mer with a greasy hydrophobic patch at its opening; it is so large it can accommodate native folding of 54-kDa GFP in its central cavity.
  • GroES is a single-ring heptamer that binds to GroEL in the presence of ATP or transition state analogues of ATP hydrolysis, such as ADP-AlF3. It's like a cover that covers GroEL (box/bottel).

GroEL/GroES may not be able to undo protein aggregates, but kinetically it competes in the pathway of misfolding and aggregation, thereby preventing aggregate formation.[1]

Group II

Group II chaperonins, found in the eukaryotic cytosol and in archaebacteria, are more poorly characterized.

TRiC (TCP-1 Ring Complex, also called CCT), the eukaryotic chaperonin, is composed of eight different though related subunits, each thought to be represented once per eight-membered ring. TRiC was originally thought to fold only the cytoskeletal proteins actin and tubulin but is now known to fold dozens of substrates.

Mm cpn (Methanococcus maripaludis chaperonin), found in the archaea Methanococcus maripaludis, is composed of sixteen identical subunits (eight per ring). It has been shown to fold the mitochondrial protein rhodanese; however, no natural substrates have yet been identified.

Group II chaperonins are not thought to utilize a GroES-type cofactor to fold their substrates. They instead contain a "built-in" lid that closes in an ATP-dependent manner to encapsulate its substrates, a process that is required for optimal protein folding activity.

Mechanism of action

Chaperonins undergo large conformational changes during a folding reaction as a function of the enzymatic hydrolysis of ATP as well as binding of substrate proteins and cochaperonins, such as GroES. These conformational changes allow the chaperonin to bind an unfolded or misfolded protein, encapsulate that protein within one of the cavities formed by the two rings, and release the protein back into solution. Upon release, the substrate protein will either be folded or will require further rounds of folding, in which case it can again be bound by a chaperonin.

Conservation of structural and functional homology

As mentioned, all cells contain chaperonins.

  • In bacteria, the archetype is the well-characterized chaperonin GroEL from E. coli.
  • In archaea, the chaperonin is called the thermosome.
  • In eukarya, the chaperonin is called CCT (also called TRiC or c-cpn).

These protein complexes appear to be essential for life in E. coli, Saccharomyces cerevisiae and higher eukaryotes. While there are differences between eukaryotic, bacterial and archaeal chaperonins the general structure and mechanism are conserved.

References

  1. ^ Fenton WA, Horwich AL (2003). "Chaperonin-mediated protein folding: fate of substrate polypeptide". Q. Rev. Biophys. 36 (2): 229–56. doi:10.1017/S0033583503003883. PMID 14686103. {{cite journal}}: Unknown parameter |month= ignored (help)

See also

External links

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