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Title: Covering complete proteomes with X-ray structures: a current snapshot

The current and the attainable coverage by X-ray structures of proteins and their functions on the scale of the ‘protein universe’ are estimated. A detailed analysis of the coverage across nearly 2000 proteomes from all superkingdoms of life and functional annotations is performed, with particular focus on the human proteome and the family of GPCR proteins. Structural genomics programs have developed and applied structure-determination pipelines to a wide range of protein targets, facilitating the visualization of macromolecular interactions and the understanding of their molecular and biochemical functions. The fundamental question of whether three-dimensional structures of all proteins and all functional annotations can be determined using X-ray crystallography is investigated. A first-of-its-kind large-scale analysis of crystallization propensity for all proteins encoded in 1953 fully sequenced genomes was performed. It is shown that current X-ray crystallographic knowhow combined with homology modeling can provide structures for 25% of modeling families (protein clusters for which structural models can be obtained through homology modeling), with at least one structural model produced for each Gene Ontology functional annotation. The coverage varies between superkingdoms, with 19% for eukaryotes, 35% for bacteria and 49% for archaea, and with those of viruses following the coverage values of their hosts.more » It is shown that the crystallization propensities of proteomes from the taxonomic superkingdoms are distinct. The use of knowledge-based target selection is shown to substantially increase the ability to produce X-ray structures. It is demonstrated that the human proteome has one of the highest attainable coverage values among eukaryotes, and GPCR membrane proteins suitable for X-ray structure determination were determined.« less
Authors:
; ; ; ;  [1] ;  [2] ;  [1]
  1. University of Alberta, Edmonton, Alberta T6G 2V4 (Canada)
  2. Argonne National Laboratory, Argonne, IL 60439 (United States)
Publication Date:
OSTI Identifier:
22347725
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section D: Biological Crystallography; Journal Volume: 70; Journal Issue: Pt 11; Other Information: PMCID: PMC4220968; PMID: 25372670; PUBLISHER-ID: dz5333; OAI: oai:pubmedcentral.nih.gov:4220968; Copyright (c) Mizianty et al. 2014; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
Denmark
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; COVERINGS; CRYSTALLIZATION; CRYSTALLOGRAPHY; CRYSTALS; CURRENTS; INTERACTIONS; SIMULATION; STRUCTURAL MODELS