Proteomics


Proteomics

Proteomics is the large-scale study of proteins, particularly their structures and functions.cite journal |author=Anderson NL, Anderson NG |title=Proteome and proteomics: new technologies, new concepts, and new words |journal=Electrophoresis |volume=19 |issue=11 |pages=1853–61 |year=1998 |pmid=9740045 |doi=10.1002/elps.1150191103] cite journal |author=Blackstock WP, Weir MP |title=Proteomics: quantitative and physical mapping of cellular proteins |journal=Trends Biotechnol. |volume=17 |issue=3 |pages=121–7 |year=1999 |pmid=10189717| doi = 10.1016/S0167-7799(98)01245-1 ] Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells. The term "proteomics" was coined to make an analogy with genomics, the study of the genes. The word "proteome" is a blend of "prote"in" and "gen"ome". The proteome is the entire complement of proteins, including the modifications made to a particular set of proteins, produced by an organism or system. This will vary with time and distinct requirements, or stresses, that a cell or organism undergoes.

Complexity of the Problem

Proteomics is often considered the next step in the study of biological systems, after genomics. It is much more complicated than genomics, mostly because while an organism's genome is constant* the proteome differs from cell to cell. This is because distinct genes are expressed in distinct cell types, meaning that even the basic set of proteins which are produced in a cell needs to be determined.

In the past this was done by mRNA analysis, but it is now known that mRNA is not always translated into protein, and the amount of protein produced for a given amount of mRNA depends on the gene it is transcribed from and on the current physiological state of the cell. Proteomics confirms the presence of the protein and provides a direct measure of the quantity present.

* The genome of healthy cells is constant. However viral infection can add genetic material to the cell, and cancer cells undergo rapid mutations, transpositions, and expansions as the tumor grows and develops.

Examples of Post-translational Modifications

Phosphorylation

More importantly though, any particular protein may go through a wide variety of alterations, which will have critical effects to its function. For example, during cell signalling many enzymes and structural proteins can undergo phosphorylation. The addition of a phosphate to particular amino acids - most commonly tyrosine, which is accomplished by tyrosine kinases, or to serine & threonine, which is mediated by serine/threonine kinases - causes a protein to become a target for binding or interacting with a distinct set of other proteins that recognize the phosphorylated domain.

Protein phosphorylation is one of the most-studied protein modifications, and thus many "proteomic" efforts are geared to determining the set of phosphorylated proteins in a particular cell or tissue-type, under particular circumstances - because this will alert the scientist to the signaling pathways that may be active in that instance.

Ubiquitination

Ubiquitin is a small peptide that can be affixed to certain protein substrates by enzymes called E3 ubiquitin ligases. Determining which proteins are poly-ubiquitinated can be helpful in understanding how protein pathways are regulated. This is therefore an additional legitimate "proteomic" study. Similarly, once it is determined what substrates are ubiquitinated by each ligase, determining the set of ligases expressed in a particular cell type will be helpful.

Additional modifications

To list all the protein modifications that might be studied in a "Proteomics" project is to recapitulate a discussion of most of biochemistry; therefore for now a short list might help to illustrate the complexity of the problem. In addition to phosphorylation and ubiquitination, proteins can be subjected to methylation, acetylation, glycosylation, oxidation, nitrosylation, etc. Some proteins undergo ALL of these modifications, which nicely illustrates the potential complexity one has to deal with when studying protein structure and function.

Distinct Proteins are Made under Distinct Settings

Even if one is studying a particular cell type, that cell may make different sets of proteins at different times, or under different conditions. Furthermore, as mentioned, any one protein can undergo a wide range of post-translational modifications.

Therefore a "proteomics" study can get quite complex very quickly, even if the object of the study is very restricted. In the more ambitious settings, such as when a biomarker for a tumor is sought - and thus the proteomics scientist is obliged to study sera samples from multiple cancer patients - the amount of compexity that must be dealt with is as great as in any modern biological project.

Rationale for Proteomics

The key requirement in understanding protein function is to learn to correlate the vast array of potential protein modifications to particular phenotypic settings, and then determine if a particular post-translational modification is required for a function to occur.

Limitations to Genomic Study

Scientists are very interested in proteomics because it gives a much better understanding of an organism than genomics. First, the level of transcription of a gene gives only a rough estimate of its level of expression into a protein. An mRNA produced in abundance may be degraded rapidly or translated inefficiently, resulting in a small amount of protein. Second, as mentioned above many proteins experience post-translational modifications that profoundly affect their activities; for example some proteins are not active until they become phosphorylated. Methods such as phosphoproteomics and glycoproteomics are used to study post-translational modifications. Third, many transcripts give rise to more than one protein, through alternative splicing or alternative post-translational modifications. Finally, many proteins form complexes with other proteins or RNA molecules, and only function in the presence of these other molecules.

Methods of studying proteins

Determining proteins which are post-translationally modified

One way in which a particular protein can be studied is to develop an antibody which is specific to that modification. For example, there are antibodies which only recognize certain proteins when they are tyrosine-phosphorylated; also, there are antibodies specific to other modifications. These can be used to determine the set of proteins that have undergone the modification of interest.

For sugar modifications, such as glycosylation of proteins, certain lectins have been discovered which bind sugars. These too can be used.

A more common way to determine post-translational modification of interest is to subject a complex mixture of proteins to electrophoresis in "two-dimensions", which simply means that the proteins are electrophoresed first in one direction, and then in another... this allows small differences in a protein to be visualized by separating a modified protein from its unmodified form. This methodology is known as "two-dimensional gel electrophoresis".

Determining the existence of proteins in complex mixtures

Classically, antibodies to particular proteins or to their modified forms have been used in biochemistry and cell biology studies. These are among the most common tools used by practicing biologists today.

For more quantitative determinations of protein amounts, techniques such as ELISAs can be used.

For proteomic study, more recent techniques such as Matrix-assisted laser desorption/ionization have been employed for rapid determination of proteins in particular mixtures.

Establishing protein-protein interactions

Most proteins function in collaboration with other proteins, and one goal of proteomics is to identify which proteins interact. This is especially useful in determing potential partners in cell signalling cascades.

Several methods are available to probe protein-protein interactions. The traditional method is yeast two-hybrid analysis. New methods include protein microarrays, immunoaffinity chromatography followed by mass spectrometry, and combinations of experimental methods such as phage display and computational methods.

Practical Applications of Proteomics

One of the most promising developments to come from the study of human genes and proteins has been the identification of potential new drugs for the treatment of disease. This relies on genome and proteome information to identify proteins associated with a disease, which computer software can then use as targets for new drugs. For example, if a certain protein is implicated in a disease, its 3D structure provides the information to design drugs to interfere with the action of the protein. A molecule that fits the active site of an enzyme, but cannot be released by the enzyme, will inactivate the enzyme. This is the basis of new drug-discovery tools, which aim to find new drugs to inactivate proteins involved in disease. As genetic differences among individuals are found, researchers expect to use these techniques to develop personalized drugs that are more effective for the individual.

A computer technique which attempts to fit millions of small molecules to the three-dimensional structure of a protein is called "virtual ligand screening". The computer rates the quality of the fit to various sites in the protein, with the goal of either enhancing or disabling the function of the protein, depending on its function in the cell. A good example of this is the identification of new drugs to target and inactivate the HIV-1 protease. The HIV-1 protease is an enzyme that cleaves a very large HIV protein into smaller, functional proteins. The virus cannot survive without this enzyme; therefore, it is one of the most effective protein targets for killing HIV.

Biomarkers

Understanding the proteome, the structure and function of each protein and the complexities of protein-protein interactions will be critical for developing the most effective diagnostic techniques and disease treatments in the future.

An interesting use of proteomics is using specific protein biomarkers to diagnose disease. A number of techniques allow to test for proteins produced during a particular disease, which helps to diagnose the disease quickly. Techniques include western blot, immunohistochemical staining, enzyme linked immunosorbent assay (ELISA) or mass spectrometry. The following are some of the diseases that have characteristic biomarkers that physicians can use for diagnosis:

Alzheimer's Disease

In Alzheimer’s disease, elevations in beta secretase create amyloid/beta-protein, which causes plaque to build up in the patient's brain, which is thought to play a role in dementia.Fact|date=August 2008 Targeting this enzyme decreases the amyloid/beta-protein and so slows the progression of the disease. A procedure to test for the increase in amyloid/beta-protein is immunohistochemical staining, in which antibodies bind to specific antigens or biological tissue of amyloid/beta-protein.

Heart Disease

Heart disease is commonly assessed using several key protein based biomarkers. Standard protein biomarkers for CVD include interleukin-6, interleukin-8, serum amyloid A protein, fibrinogen, and troponins. cTnI cardiac troponin I increases in concentration within 3 to 12 hours of initial cardiac injury and can be found elevated days after an acute myocardial infarction. A number of commercial antibody based assays as well as other methods are used in hospitals as primary tests for acute MI.

ee also

* proteomic chemistry
* bioinformatics
* cytomics
* genomics
* List of omics topics in biology
* metabolomics
* lipidomics
* Shotgun proteomics
* Top-down proteomics
* Bottom-up proteomics
* systems biology
* transcriptomics
* phosphoproteomics
* PEGylation

Protein databases

* UniProt
* Protein Information Resource (PIR)
* Swiss-Prot
* Protein Data Bank (PDB)
* National Center for Biotechnology Information (NCBI)
* Human Protein Reference Database
* Proteopedia The collaborative, 3D encyclopedia of proteins and other molecules.

References

Bibliography

* Belhajjame, K. et al. [http://www.allhands.org.uk/2005/proceedings/papers/525.pdf Proteome Data Integration: Characteristics and Challenges] . Proceedings of the UK e-Science All Hands Meeting, ISBN 1-904425-53-4, September 2005, Nottingham, UK.
* Twyman, R. M. 2004. Principles of proteomics. BIOS Scientific Publishers, New York. ISBN 1-85996-273-4.(covers almost all branches of proteomics)
* Westermeier, R. and T. Naven. 2002. Proteomics in practice: a laboratory manual of proteome analysis. Wiley-VCH, Weinheim. ISBN 3-527-30354-5.(focused on 2D-gels, good on detail)
* Liebler, D. C. 2002. Introduction to proteomics: tools for the new biology. Humana Press, Totowa, NJ. ISBN 0-585-41879-9 (electronic, on Netlibrary?), ISBN 0-89603-991-9 hardback, ISBN 0-89603-992-7 paperback.
* Wilkins MR, Williams KL, Appel RD, Hochstrasser DF. "Proteome research: new frontiers in functional genomics". Berlin Heidelberg, Springer Verlag; 1997, ISBN 3-540-62753-7.
* [http://www.springerlink.com/openurl.asp?genre=article&doi=10.1007/s00776-004-0878-0]
*Rediscovering Biology Online Textbook. Unit 2 Proteins and Proteomics. 1997-2006.
* Weaver. R.F. Molecular Biology. Third Edition. The McGraw-Hill Companies Inc. 2005. pgs 840-849.
* Campbell and Reece. Biology. Sixth Edition. Pearson Education Inc. 2002. pg 392-393.
* Hye A, Lynham S, Thambisetty M, et al. " Proteome-based plasma biomarkers for Alzheimer's disease." Brain 129: 3042-3050, (2006).
* Perroud B, Lee J, Valkova N, et al. "Pathway Analysis of Kidney Cancer Using Proteomics and *Metabolic Profiling." Biomed Central: 65-82, (24 November 2006).
* Macaulay IC, Carr P, Gusnanto A, et al. "Platelet Genomics and Proteomics in Human Health and Disease." The Journal of Clinical Investigation 115: 3370-3377, (December 2005).
* Rogers MA, Clarke P, Noble J, et al. "Proteomic Profiling of Urinary Proteins in Renal Cancer by Surface Enhanced Laser Desorption Ionization, and Neural-Network Analysis: Identification of Key Issues Affecting Clinical Potential Utility." Cancer Research 63: 6971-6983, (15 October 2003).
*Vasan RS. “Biomarkers of cardiovascular disease: molecular basis and practical considerations” Circulation. 2006;113:2335-2362.
* “Myocardial Infarction”. http://medlib.med.utah.edu/WebPath/TUTORIAL/MYOCARD/MYOCARD.html (Retrieved 29 Nov 2006)
* World Community Grid. http://www.worldcommunitygrid.org (Retrieved 29 Nov 2006)
* Introduction to Antibodies - Enzyme-Linked Immunosorbent Assay (ELISA). http://www.chemicon.com/resource/ANT101/a2C.asp. (Retrieved 29 Nov 2006)
* Decramer S et al "Predicting the clinical outcome of congenital unilateral ureteropelvic junction obstruction in newborn by urinary proteome analysis" Nature Medicine 2006; 12:398-400 [http://www.nature.com/nm/journal/v12/n4/abs/nm1384.html;jsessionid=3F9707D2B671CA69E12EC68E65919D60 Article]
* Mayer, U. (2008) Protein Information Crawler (PIC): Extensive spidering of multiple protein information resources for large protein sets. Proteomics, 8: 42-44 [http://www.ncbi.nlm.nih.gov/pubmed/18095364?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum PubMed]

External links

* [http://pcarvalho.com/patternlab PatternLab for proteomics: a tool for analyzing shotgun proteomic spectral counting data]
* [http://www.zoo.uni-heidelberg.de/mfa/PIC/index.htm Protein Information Crawler (PIC)] - Software for extensive spidering of multiple protein information resources for large protein sets
* [http://www.springerprotocols.com Springer Protocols in proteomics]


Wikimedia Foundation. 2010.

Look at other dictionaries:

  • Proteomics —   [prəʊtɪ ɔmɪks, englisch], Proteombiologie, Wissenschaftszweig, der sich mit der globalen Analyse zellulärer Proteine (Proteom), deren Struktur, Funktion und Wechselwirkungen befasst, um die Rolle normaler Proteine und die Schlüsselrolle… …   Universal-Lexikon

  • proteomics —  Proteomics  Протеомика (от протеин и геномика)   Наука, основным предметом изучения которой являются белки (протеины) и их взаимодействия в живых организмах, в том числе в человеческом. Учёные, работающие в области протеомики, исследуют… …   Толковый англо-русский словарь по нанотехнологии. - М.

  • Proteomics — Die Proteomik (englisch: proteomics) umfasst die Erforschung des Proteoms, das heißt der Gesamtheit aller in einer Zelle oder einem Lebewesen unter definierten Bedingungen und zu einem definierten Zeitpunkt vorliegenden Proteine. Das Proteom ist… …   Deutsch Wikipedia

  • Proteomics — The study of the proteome, all of the proteins produced by a given species. (The proteome is to protein as the genome is to DNA.) The term proteome was first coined from the PROTEin complement of the genOME in the mid 1990s by Marc Wilkins, a… …   Medical dictionary

  • proteomics — proteomika statusas T sritis chemija apibrėžtis Visiškas visų tam tikro organizmo sintetinamų baltymų ištyrimas. atitikmenys: angl. proteomics rus. протеомика …   Chemijos terminų aiškinamasis žodynas

  • proteomics — proteomika statusas T sritis augalininkystė apibrėžtis Mokslas, tiriantis individų baltymų sandarą, funkcijas ir tarpusavio sąveiką. atitikmenys: angl. proteomics rus. протеомика …   Žemės ūkio augalų selekcijos ir sėklininkystės terminų žodynas

  • proteomics — noun plural but singular in construction Date: 1997 a branch of biotechnology concerned with applying the techniques of molecular biology, biochemistry, and genetics to analyzing the structure, function, and interactions of the proteins produced… …   New Collegiate Dictionary

  • proteomics — noun The branch of molecular biology that studies the set of proteins expressed by the genome of an organism See Also: proteome, proteomicist …   Wiktionary

  • proteomics — plural noun [treated as sing.] the branch of molecular biology concerned with determining the proteome. Derivatives proteomic adjective …   English new terms dictionary

  • proteomics — pro·te·o·mics …   English syllables


Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”

We are using cookies for the best presentation of our site. Continuing to use this site, you agree with this.