Multi-scale sequence correlations increase proteome structural disorder and promiscuity

Ariel Afek, Eugene I. Shakhnovich, David B. Lukatsky

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Numerous experiments demonstrate a high level of promiscuity and structural disorder in organismal proteomes. Here, we ask the question what makes a protein promiscuous, that is, prone to nonspecific interactions, and structurally disordered. We predict that multi-scale correlations of amino acid positions within protein sequences statistically enhance the propensity for promiscuous intra- and inter-protein binding. We show that sequence correlations between amino acids of the same type are statistically enhanced in structurally disordered proteins and in hubs of organismal proteomes. We also show that structurally disordered proteins possess a significantly higher degree of sequence order than structurally ordered proteins. We develop an analytical theory for this effect and predict the robustness of our conclusions with respect to the amino acid composition and the form of the microscopic potential between the interacting sequences. Our findings have implications for understanding molecular mechanisms of protein aggregation diseases induced by the extension of sequence repeats.

Original languageEnglish
Pages (from-to)439-449
Number of pages11
JournalJournal of Molecular Biology
Volume409
Issue number3
DOIs
StatePublished - 10 Jun 2011

Keywords

  • AP/MS
  • PPI
  • Y2H
  • affinity purification/mass spectrometry
  • protein-protein interaction
  • yeast two-hybrid

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