Proteomics

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Structure of hemoglobin

The proteomics ( English proteomics ) comprises the research of the proteome with biochemical methods. The proteome comprises the entirety of all proteins present in a cell or a living being under defined conditions and at a defined point in time . In contrast to the rather static genome, the proteome and also the transcriptome are dynamic and can therefore change their qualitative and quantitative protein composition due to changed conditions (environmental factors, temperature, gene expression, drug administration, etc.). The dynamics of the proteome can be visualized in the following example. A caterpillar and the butterfly that emerges from it contain the same genome, but still differ externally due to a different proteome. The same is true for a tadpole and the frog that emerges from it. The changes in the proteome can sometimes occur very quickly, for example through post-translational modifications such as phosphorylation and dephosphorylation of proteins, which play a very important role in signal transduction .

Proteomics tries to catalog all proteins in the organism and to decipher their functions. The blueprints for proteins can be found in the genetic make-up. If the genetic material DNA only stores information, the protein molecules made up of amino acids fulfill a variety of tasks. They are the basic substance of life and defend z. B. as antibodies from diseases, and as enzymes, among other things , enable metabolism and ensure movement with the skeleton, tendons and muscles.

etymology

The word proteome comes from the Australian researcher Marc Wilkins and was mentioned for the first time on a slide in his lecture at the congress 2D Electrophoresis: from protein maps to genomes , on September 5, 1994 in Siena . The wording on the slide read: “ Proteome: the PROTEin complement expressed by a genOME, cell or tissue. ”(German:“ Proteome: the PROTEin complement that is expressed by the genome of a cell or tissue ”). The congress still takes place every two years (as of 2012) under the direction of Luca Bini and has been called since the famous slide by Marc Wilkins: From Genome to Proteome .

Research focus HUPO and DGPF

Similar to the Human Genome Organization (HUGO), the researchers of the International Human Proteome Organization (HUPO) share the work that arises worldwide. Germany is concentrating on research into brain proteins. In Germany, leading protein and proteomics scientists have also joined forces in the German Society for Proteome Research (DGPF) since 2001 in order to make optimal use of research capacities.

Sub-areas

The proteome in the 2D gel

The main areas are the elucidation of protein-protein interactions , which mainly depend on the tertiary and quaternary structures of proteins and the interactions between their domains . Protein purification and quantitative analysis of protein expression also belong to the field of proteomics. It thus supplements the data obtained in the gene expression analysis and provides information about the components of metabolic pathways and molecular control loops. The protein engineering allows modification of functions of recombinant proteins to adapt its properties.

The key techniques of proteomics thus support the elucidation of the function and the 3-D protein structure and the identification of individual proteins in mixtures.

Since all metabolic processes take place through proteins, therapeutic approaches such as new active ingredients against cancer , infections and certain nervous diseases are based on them. Ailments such as sickle cell anemia , Alzheimer's disease , Huntington 's disease or Creutzfeldt-Jakob disease are based on incorrectly formed and clumping proteins. If it is known which protein is responsible for a malfunction, it is possible to specifically develop a small molecule which docks onto this protein and prevents further malfunction. In industry, recombinant proteins are used in the form of detergent enzymes and biological pesticides. Biologists hope to gain better insights into how living beings work and life as such. The biophysicists expect a “molecular anatomy ”.

Systems biology

Systems biology is a new area of ​​research that builds on proteomics . This no longer tries alone the individual parts z. B. to consider a cell, but tries to describe the interaction of all individual parts within a system and its environment. In addition to proteomics v. a. mathematical models that simulate the system in silico (i.e. in computer models).

Paleoproteomics

In addition to “old” DNA , fossil proteins can occasionally be isolated from fossil bones . B. enable conclusions to be drawn about their affiliation to a certain biological species . The paleoproteomics based on this (from the Greek παλαιός palaiós , "old") benefits in particular from the fact that some proteins are more stable than DNA for a longer period of time . In 2016, the working group of Jean-Jacques Hublin from the Max Planck Institute for Evolutionary Anthropology, using collagen samples around 40,000 years old, clarified that the archaeological culture of Châtelperronia is associated with the Neanderthals and not with anatomically modern humans ( Homo sapiens ). In 2019, fossil proteins from dentin from the Xiahe lower jaw , discovered in the Baishiya Cave in the highlands of Tibet, demonstrated that it is attributable to the Denisova people , and a few months later, 1.9 million year old dentin samples confirmed that the genus Gigantopithecus is an extinct "sister" taxon of the orangutans . As early as 2015, collagen analyzes revealed a closer relationship between the " South American ungulates " and the odd- toed ungulates , namely Macrauchenia and Toxodon , which still occurred in the late Pleistocene . Previously, the exact relationships between the "South American ungulates" and other ungulate groups were unclear and the subject of scientific debate. For the extinct rhinoceros representative Stephanorhinus , there was a closer relationship to the woolly rhinoceros and thus to a closer circle of relatives around today's Sumatran rhinoceros on the basis of around 200,000 to 400,000 and 1.8 million year old proteomes . The position could also be proven by genetic studies and had previously been accepted for anatomical reasons. Also in 2019, studies on proteins contributed to the systematic reorganization of fossil and modern sloths .

In 2015, for example, a study on the 80-million-year-old bones of Brachylophosaurus canadensis , which belongs to the group of duck-billed dinosaurs , received worldwide media attention , in which peptides were detected that - due to their similarity to peptides from today's hens and ostriches - were interpreted as remains of blood vessels.

Problems and trends

After some sobering experiences with genetic methods such as microarray analysis, some scientists are also somewhat skeptical about proteome research. Friedrich Lottspeich from the Max Planck Institute for Biochemistry in Martinsried , President of the German Society for Proteome Research (DGPF), warns against exaggerated hopes:

"For the human area, research is actually still too complex at the moment anyway [...] But again, of course, nobody wants to spend money on an analysis of yeast, which would be a good model system."

The complexity results from the many possibilities: According to Friedrich Lottspeich, humans have an estimated several hundred thousand to millions of different proteins. A single gene produces an average of five to ten proteins, in some cases several hundred. Understanding this complexity in full is a challenge that current methods are not yet able to cope with. On the other hand, proteome research is developing rapidly. This is mainly due to the constant improvement in mass spectrometers , which are becoming more and more precise, sensitive and faster.

Another important step is the development of quantitative methods, such as the SILAC , iTRAQ , TMT or ICAT processes based on the use of stable isotopes or the MeCAT metal coding, in which metals of different weights are used to mark proteins and peptides from different protein samples. The latter allows for the first time in the multiplex approach the proteome-wide use of ultra-sensitive elemental mass spectrometry ( ICP-MS ) (detection limit in the ppt to lower ppq range), which allows a more than 2 to 5 orders of magnitude higher sensitivity in protein quantification and a linear dynamic measuring range of at least 6 to 8 orders of magnitude having. In contrast to the other methods, which “only” quantify relatively at the peptide level, MeCAT advantageously allows relative and even absolute quantification at the protein level, making protein species such as post-translationally modified proteins more accessible to quantification. Calibration of the ICP-MS is done with protein / peptide un -dependent metal standards. There is therefore no need for protein-specific standard peptides.

If quantitative proteome analysis is combined with other biological methods, statements can also be made about the function of proteins (e.g. protein-protein interaction or post-translational modifications ). Modern proteome research therefore goes far beyond the mere cataloging of proteins and tries to understand complex mechanisms.

See also

literature

  • David P. Clark, Nanette J. Pazdernik: Molecular Biotechnology. Basics and Applications . Spectrum Akademischer Verlag, Heidelberg 2009, ISBN 3-8274-2128-4 , p. 263-294 .
  • Hubert Rehm : Protein Biochemistry, Proteomics (=  The Experimenter ). 5th edition. Spektrum Akademischer Verlag, Heidelberg 2006, ISBN 3-8274-1726-0 .
  • Hans Gerd Nothwang, Steven E. Pfeiffer: Proteomics of the Nervous System . Wiley-VCH, Weinheim 2008, ISBN 978-3-527-31716-5 .
  • Jörg von Hagen: Proteomics Sample Preparation . VCH-Wiley, Weinheim 2008, ISBN 978-3-527-31796-7 .
  • Sabine Fischer (Ed.): Functional Proteomics. Recognize the causes of illness at an early stage and treat them specifically . Elsevier, Munich 2008, ISBN 978-3-437-57920-2 .
  • Friedrich Lottspeich , Haralabos Zorbas: Bioanalytics . Spektrum Akademischer Verlag, Heidelberg 1998, ISBN 978-3-8274-0041-3 .
  • Scott D. Patterson, Ruedi H. Aebersold: Proteomics: the first decade and beyond . In: Nature Genetics . tape 33 , March 2003, p. 311–323 , doi : 10.1038 / ng1106 (review, free full text).

Web links

Wiktionary: Proteomics  - explanations of meanings, word origins, synonyms, translations

Individual evidence

  1. ^ Definition of proteome
  2. ^ Website of the congress in Siena
  3. ↑ Rolf Apweiler, Charalampos Aslanidis, Thomas Deufel, Andreas Gerstner, Jens Hansen, Dennis Hochstrasser, Roland Kellner, Markus Kubicek, Friedrich Lottspeich, Edmund Maser, Hans-Werner Mewes, Helmut E. Meyer, Stefan Müllner, Wolfgang Mutter, Michael Neumaier, Peter Nollau, Hans G. Nothwang, Fredrik Ponten, Andreas Radbruch, Knut Reinert, Gregor Rothe, Hannes Stockinger, Attila Tárnok, Mike J. Taussig, Andreas Thiel, Joachim Thiery, Marius Ueffing, Günther Valet, Joel Vandekerckhove, Christoph Wagener, Oswald Wagner, Gerd Schmitz: Approaching clinical proteomics. Current state and future fields of application in cellular proteomics . In: Cytometry. Part A . tape 75 , no. 10 , October 2009, p. 816-832 , doi : 10.1002 / cyto.a.20779 , PMID 19739086 (review).
  4. ↑ Frido Welker, Mateja Hajdinjak, Sahra Talamo, [...] and Jean-Jacques Hublin: Palaeoproteomic evidence identifies archaic hominins associated with the Châtelperronian at the Grotte du Renne. In: PNAS. Volume 113, No. 40, 2016, pp. 11162–11167, doi: 10.1073 / pnas.1605834113
    Paleoproteomics helps differentiate between modern humans and Neanderthals. On: mpg.de from September 16, 2016
  5. ↑ Eye and eye with the Neanderthal man. In: Max Plack Research. No. 2, 2017, pp. 18-25.
  6. ↑ Fahu Chen et al .: A late Middle Pleistocene Denisovan mandible from the Tibetan plateau. In: Nature. Online pre-publication from May 1, 2019, doi: 10.1038 / s41586-019-1139-x
  7. ↑ Frido Welker et al .: Enamel proteome shows that Gigantopithecus was an early diverging pongine. In: Nature. Online advance publication of November 13, 2019, doi: 10.1038 / s41586-019-1728-8 .
    Oldest molecular information to date illuminates the history of extinct Gigantopithecus. On: eurekalert.org of November 13, 2019.
  8. ↑ Frido Welker et al. Ancient proteins resolve the evolutionary history of Darwin's South American ungulates. In: Nature. Volume 522, 2015, pp. 81–84, doi: 10.1038 / nature14249 .
  9. ↑ Michael Buckley: Ancient collagen reveals evolutionary history of the endemic South American 'ungulates'. In: Proceedings of the Royal Society B. Volume 282, 2015, S. 20142671 doi: 10.1098 / rspb.2014.2671 .
  10. ↑ Frido Welker et al .: Middle Pleistocene protein sequences from the rhinoceros genus Stephanorhinus and the phylogeny of extant and extinct Middle / Late Pleistocene Rhinocerotidae. In: PeerJ. Volume 5, 2017, p. E3033, doi: 10.7717 / peerj.3033 .
  11. ↑ Enrico Cappellini et al .: Early Pleistocene enamel proteome from Dmanisi resolves Stephanorhinus phylogeny. In: Nature. Volume 574, 2019, pp. 103-107, doi: 10.1038 / s41586-019-1555-y .
  12. ↑ Irina V. Kirillova et al .: Discovery of the skull of Stephanorhinus kirchbergensis (Jäger, 1839) above the Arctic Circle. In: Quaternary Research. Volume 88, 2017, pp. 537-550, doi: 10.1017 / qua.2017.53 .
  13. ↑ Samantha Presslee et al .: Palaeoproteomics resolves sloth relationships. In: Nature Ecology & Evolution. Volume 3, 2019, pp. 1121-1130, doi: 10.1038 / s41559-019-0909-z .
  14. ↑ Timothy P. Cleland et al .: Mass Spectrometry and Antibody-Based Characterization of Blood Vessels from Brachylophosaurus canadensis. In: Journal of Proteome Reseaarch. Volume 14, No. 12, 2015, pp. 5252–5262, doi: 10.1021 / acs.jproteome.5b00675
    Bone splinters: Researchers discover dinosaur blood vessels. On: spiegel.de from December 2, 2015
  15. ^ Friedrich Lottspeich: Introduction to proteomics . In: Jörg Reinders, Albert Sickmann (Ed.): Proteomics. Methods and Protocols (=  Methods in Molecular Biology . Volume 564 ). Humana Press, Totowa 2009, ISBN 978-1-60761-156-1 , pp. 3-10 , doi : 10.1007 / 978-1-60761-157-8_1 , PMID 19544014 (review).
  16. Jump up ↑ Pier Giorgio Righetti, Natascia Campostrini, Jennifer Pascali, Mahmoud Hamdan, Hubert Astner: Quantitative proteomics. A review of different methodologies . In: European Journal of Mass Spectrometry . tape 10 , no. 3 . Chichester (England) 2004, p. 335-348 , doi : 10.1255 / ejms.600 , PMID 15187293 (review).
  17. ^ Friedrich Lottspeich, Josef Kellermann: ICPL labeling strategies for proteome research . In: Kris Gevaert, Joël Vandekerckhove (Ed.): Gel-Free Proteomics. Methods and Protocols (=  Methods in Molecular Biology . Volume 753 ). Humana Press, Totowa 2011, ISBN 978-1-61779-147-5 , pp. 55-64 , doi : 10.1007 / 978-1-61779-148-2_4 , PMID 21604115 .