Utilization of protein intrinsic disorder knowledge in structural proteomics

Christopher J. Oldfield, Bin Xue, Ya Yue Van, Eldon L. Ulrich, John L. Markley, A. Keith Dunker, Vladimir N. Uversky

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Intrinsically disordered proteins (IDPs) and proteins with long disordered regions are highly abundant in various proteomes. Despite their lack of well-defined ordered structure, these proteins and regions are frequently involved in crucial biological processes. Although in recent years these proteins have attracted the attention of many researchers, IDPs represent a significant challenge for structural characterization since these proteins can impact many of the processes in the structure determination pipeline. Here we investigate the effects of IDPs on the structure determination process and the utility of disorder prediction in selecting and improving proteins for structural characterization. Examination of the extent of intrinsic disorder in existing crystal structures found that relatively few protein crystal structures contain extensive regions of intrinsic disorder. Although intrinsic disorder is not the only cause of crystallization failures and many structured proteins cannot be crystallized, filtering out highly disordered proteins from structure-determination target lists is still likely to be cost effective. Therefore it is desirable to avoid highly disordered proteins from structure-determination target lists and we show that disorder prediction can be applied effectively to enrich structure determination pipelines with proteins more likely to yield crystal structures. For structural investigation of specific proteins, disorder prediction can be used to improve targets for structure determination. Finally, a framework for considering intrinsic disorder in the structure determination pipeline is proposed.

Original languageEnglish (US)
Pages (from-to)487-498
Number of pages12
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1834
Issue number2
DOIs
StatePublished - Feb 1 2013

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Keywords

  • Intrinsically disordered protein
  • Proteomics
  • Structural genomics
  • Structural proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Analytical Chemistry
  • Molecular Biology

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