Molecular Principles of the Interactions of Disordered Proteins

Bálint Mészáros, Peter Tompa, I. Simon, Z. Dosztányi

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

Thorough knowledge of the molecular principles of protein-protein recognition is essential to our understanding of protein function at the cellular level. Whereas interactions of ordered proteins have been analyzed in great detail, complexes of intrinsically unstructured/disordered proteins (IUPs) have hardly been addressed so far. Here, we have collected a database of 39 complexes of experimentally verified IUPs, and compared their interfaces with those of 72 complexes of ordered, globular proteins. The characteristic differences found between the two types of complexes suggest that IUPs represent a distinct molecular implementation of the principles of protein-protein recognition. The interfaces do not differ in size, but those of IUPs cover a much larger part of the surface of the protein than for their ordered counterparts. Moreover, IUP interfaces are significantly more hydrophobic relative to their overall amino acid composition, but also in absolute terms. They rely more on hydrophobic-hydrophobic than on polar-polar interactions. Their amino acids in the interface realize more intermolecular contacts, which suggests a better fit with the partner due to induced folding upon binding that results in a better adaptation to the partner. The two modes of interaction also differ in that IUPs usually use only a single continuous segment for partner binding, whereas the binding sites of ordered proteins are more segmented. Probably, all these features contribute to the increased evolutionary conservation of IUP interface residues. These noted molecular differences are also manifested in the interaction energies of IUPs. Our approximation of these by low-resolution force-fields shows that IUPs gain much more stabilization energy from intermolecular contacts, than from folding, i.e. they use their binding energy for folding. Overall, our findings provide a structural rationale to the prior suggestions that many IUPs are specialized for functions realized by protein-protein interactions.

Original languageEnglish
Pages (from-to)549-561
Number of pages13
JournalJournal of Molecular Biology
Volume372
Issue number2
DOIs
Publication statusPublished - Sep 14 2007

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Intrinsically Disordered Proteins
Proteins

Keywords

  • disorder-to-order transition
  • intrinsically unstructured proteins
  • molecular recognition
  • protein-protein interactions
  • protein-protein interface

ASJC Scopus subject areas

  • Virology

Cite this

Molecular Principles of the Interactions of Disordered Proteins. / Mészáros, Bálint; Tompa, Peter; Simon, I.; Dosztányi, Z.

In: Journal of Molecular Biology, Vol. 372, No. 2, 14.09.2007, p. 549-561.

Research output: Contribution to journalArticle

Mészáros, Bálint ; Tompa, Peter ; Simon, I. ; Dosztányi, Z. / Molecular Principles of the Interactions of Disordered Proteins. In: Journal of Molecular Biology. 2007 ; Vol. 372, No. 2. pp. 549-561.
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