Structural Proteomics: Large‐Scale Studies

Abstract

Proteins have many different functions in biological systems, and the molecular functions of proteins are dependent on their three‐dimensional structures. Mapping protein structures is therefore an important strategy in understanding gene and protein function. Structural proteomics or structural genomics refers to systematic efforts to functionally annotate protein molecular structures of whole or selected parts of genomes and/or proteomes. Structural proteomics studies have significantly added to our knowledge of protein structures over the past few years and a large fraction of available protein structures in public databases result from high‐throughput structural proteomics studies. Although structural proteomics techniques are continually being improved, significant challenges remain in protein expression and crystallisation and in particular for solving protein structures for challenging classes of protein such as membrane proteins.

Key Concepts

  • Protein function is directly linked to the three‐dimensional structure of the protein.
  • Structural proteomics refers to large‐scale mapping of protein structures.
  • Techniques such as protein crystallisation and X‐ray bombardment allow the three‐dimensional arrangement of atoms in protein molecules to be determined.
  • Technical and biological challenges remain in structural proteomics – in particular for certain classes of proteins such as proteins that span membranes. Large‐scale structural proteomics is an enabling technology for systems biology.

Keywords: structural genomics; high throughput; protein; X‐ray; nuclear magnetic resonance methods; crystallography; systems biology

Figure 1. Experimental flow in structural proteomics, the current bottlenecks and important technology developments.
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Further Reading

Kloppmann E, Punta M and Rost B (2012) Structural genomics plucks high‐hanging membrane proteins. Current Opinion in Structural Biology 22 (3): 326–332. DOI: 10.1016/j.sbi.2012.05.002.

Lu H‐C, Fornili A and Fraternali F (2013) Protein–protein interaction networks studies and importance of 3D structure knowledge. Expert Review of Proteomics 10 (6): 511–520. DOI: 10.1586/14789450.2013.856764.

Slabinski L, Jaroszewski L, Rodrigues APC, et al. (2007) The challenge of protein structure determination – lessons from structural genomics. Protein Science: A Publication of the Protein Society 16 (11): 2472–2482. DOI: 10.1110/ps.073037907.

Stevens RC and Yates JR (2007) Proteomics: You Say Functional, I Say Structural. Journal of Proteome Research 6 (3): 927–927.

Terwilliger TC, Stuart D and Yokoyama S (2009) Lessons from structural genomics. Annual Review of Biophysics 38: 371–383. DOI: 10.1146/annurev.biophys.050708.133740.

Web Links

The Protein Databank (PDB) – A worldwide repository for the processing and distribution of 3‐D biological macromolecular structure data. http://www.rcsb.org/

CATH – Protein Structure Classification. CATH is a database for classification of protein domain structures into families. http://www.cathdb.info

DALI – a database of structural alignments of all proteins in the protein structure database. http://ekhidna.biocenter.helsinki.fi/dali

ProFunc – server for predicting protein function from structure. http://www.ebi.ac.uk/thornton‐srv/databases/profunc

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Ewing, Rob M, and Doyle, Declan A(Jun 2015) Structural Proteomics: Large‐Scale Studies. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006220.pub2]