Post-translational modification
Post-translational protein modifications ( PTM ) are changes in proteins that occur after translation . Most are triggered by the organism or by the cells themselves.
Proteins are often involved in these processes, by modifying genes ( modifier genes ) are encoded. The gene products of such modification genes can be formed or functionalized depending on environmental factors and influence proteins accordingly.
While some of the processes take place directly at the point of origin, others take place in certain cell organelles, while others take place outside the producing cell.
In addition to intended protein changes, however, unwanted protein modifications also occur. Assuming that the transcription and translation machinery works when transcribing the genes via the mRNA to the proteins with error rates of 1/1000 nucleotides or 1 / 10,000 amino acids, the incorporation of incorrect amino acids will produce significant amounts of mistranslated polypeptide chains. The proportion of mistranslated proteins that are actually not changed post-translationally, but cotranslationally, can be increased by the presence of streptomycin (disruption of the ribosome ) or by a lack of individual amino acids.
In addition, protein chains can be damaged, changed or denatured by radicals , high-energy radiation or other proteins (see prions ) and form folding isoforms that no longer correspond to the original conformation and cannot fulfill the intended function.
Categories of post-translational modification
Cells have a multitude of possibilities to process and change their proteins. To do this, they have a large number of enzymes that are specially formed by the cell for protein modification. Protein modification processes can take place constitutively or they can be influenced by environmental influences or other parameters. The modification can be the N - or C -terminus or a side chain modification done. About 300 different post-translational modifications have been described. The following processes that lead to new protein species were analyzed:
Spin-offs
- Cleavage of the N -terminal formyl residue by deformylase . Every newly synthesized protein (in prokaryotes ) initially contains an N -terminal formylmethionine (methionine in eukaryotes ), which is always incorporated first during translation and whose formyl residue is subsequently split off by the deformylase. Any formyl residue that is still present indicates that the synthesis of the protein molecule has just ended.
- the cleavage of the methionyl residue at the N terminus of newly synthesized proteins by methionylaminopeptidase . In bacteria it was observed that the size of the following amino acid influences the cleavage behavior of the N -terminal methionine. The larger the second amino acid, the less likely it is that the starting methionine will be split off.
- the targeted splitting off of signal sequences (such as protocolagen to collagen)
- the selective cutting out of partial sequences ( e.g. proinsulin to insulin, generally precursor proteins )
- Protein inactivation and fragmentation by proteolysis involving proteases
Inorganic Groups
- Phosphorylation by protein kinases to form phosphoproteins
- Hydroxylation of proline residues to hydroxyproline residues (mainly in collagen , but also in elastin , argonaut 2 , hypoxia-induced factor α, etc.)
- Hydroxylation of lysine residues to hydroxylysine residues (often starting point for glycosylation, in collagen also for subsequent cross-links)
- Iodination and bromination , v. a. in molluscs, bovine neuropeptide B
- nitration
- S-nitrosylation
- Sulfation
Organic groups
- Glycosylations ( glycoproteins ); N -glycosidic in the endoplasmic reticulum , O -glycosidic in the Golgi apparatus , e.g. B. fucosylation , mannosylation and sialylation , C -glycosidic as C -mannosylation
- Formylation in prokaryotes in formylmethionine
- Acetylation by acetyltransferases on lysines , e.g. B. Histone Acetyl Transferase
- Propionylation
- Butyrylation
- Crotonylation
- Malonylation
- Glutarylation
- Succinylation on lysines with succinate
- Succination on cysteines
- Attachment of a citrulline residue ( CXCL10 , filaggrin , several histones )
- Methylation , e.g. B. Asymmetric dimethylarginine , histone methyltransferases on lysines
- Biotinylation
- Amidation , e.g. B. at the C terminus
- Ubiquitinylation on lysines for proteolysis
- SUMO proteins ( Small Ubiquitin-related Modifier ) for proteolysis
- Pupylation on lysines for proteolysis in prokaryotes
- Urmylation
- Neddylation
- Sampylation in archaea
- ADP ribosylation , e.g. B. by the poly (ADP-ribose) polymerase 1
- Addition of glutathione via a disulfide bridge ( beta-crystallin , glutaredoxin-2 )
- Binding to quinones , mainly in electron transport
- Flavin modifications, e.g. B. flavin mononucleotide or flavin adenine dinucleotide
- Heme modifications, e.g. B. Heme C on lysines
- Retinylidene modification as a Schiff base from retinal in opsins
- Adenylation
Organic lipid groups
These lipid anchor modifications cause adsorption to the cell membrane .
- GPI anchor
- Lipid modifications by prenylation to lipoproteins , e.g. B. Farnesylation , Geranylgeranylation
- Lipid modifications by long-chain acylation with fatty acids to lipoproteins , e.g. B. Palmitoylation and Myristoylation
- Lipoic acid modification, e.g. B. on the pyruvate dehydrogenase by the lipoate protein ligase
Adding bindings
- the formation of disulfide bridges between neighboring cysteine residues to cystine (such as insulin )
- the change in folding by chaperones
- the formation of protein complexes from subunits (such as hemoglobin)
- the formation of solid structures via covalent cross-links (such as collagen fibrils)
- Formation of an isopeptide bond , e.g. in blood clotting
- Formation of a thioester bond between Cys and Asn / Gln (including complement component C3 )
- Formation of a thioether bond between Cys and Ser / Thr ( amatoxins and others)
Binding to larger molecules
- the connection with coenzymes and prosthetic groups (e.g. heme + hemoglobin)
- Covalent binding to DNA and RNA ( viruses only )
- covalent anchoring to peptidoglycans in bacterial cell walls
Change of individual amino acids
- L- / D- isomerization : the change of a L -amino acid to D -amino acid , been established in several animal groups (excluding the poisons amphibians , arthropods , molluscs and platypus )
- Vitamin K -dependent carboxylation of a glutamate residue to γ-carboxyglutamate (coagulation and calcified tissue) by γ-glutamyl carboxylase
- Conversion of a lysine to hypusine ( N -ε- (4-aminobutyl) lysine). Only known protein: eIF-5A
- Oxidation of individual amino acid residues (crystalline)
- Ring closure of glutamic acid to pyroglutamic acid
- Formation of formylglycine of cysteine at Sulfatases
Miscellaneous
- Formation of a stable radical (bacteria)
- the binding ( complexation ) of ions and low molecular weight substances
literature
- H. Lin, X. Su, B. He: Protein lysine acylation and cysteine succination by intermediates of energy metabolism. In: ACS chemical biology. Volume 7, number 6, June 2012, ISSN 1554-8937 , pp. 947-960, doi : 10.1021 / cb3001793 , PMID 22571489 , PMC 3376250 (free full text).
Web links
- UniProt Keyword: PTM
- UniProt: Controlled vocabulary of posttranslational modifications (PTM)
Individual evidence
- ^ S. Lee: Post-translational modification of proteins in toxicological research: focus on lysine acylation. In: Toxicological research. Volume 29, number 2, June 2013, pp. 81–86, doi : 10.5487 / TR.2013.29.2.081 , PMID 24278632 , PMC 3834447 (free full text).