Protein-Protein Interactions Mediated by Helical Tertiary Structure Motifs

Andrew M. Watkins, Michael G. Wuo, Paramjit Arora

Research output: Contribution to journalArticle

Abstract

The modulation of protein-protein interactions (PPIs) by means of creating or stabilizing secondary structure conformations is a rapidly growing area of research. Recent success in the inhibition of difficult PPIs by secondary structure mimetics also points to potential limitations, because often, specific cases require tertiary structure mimetics. To streamline protein structure-based inhibitor design, we have previously described the examination of protein complexes in the Protein Data Bank where α-helices or β-strands form critical contacts. Here, we examined coiled coils and helix bundles that mediate complex formation to create a platform for the discovery of potential tertiary structure mimetics. Though there has been extensive analysis of coiled coil motifs, the interactions between pre-formed coiled coils and globular proteins have not been systematically analyzed. This article identifies critical features of these helical interfaces with respect to coiled coil and other helical PPIs. We expect the analysis to prove useful for the rational design of modulators of this fundamental class of protein assemblies.

Original languageEnglish (US)
Pages (from-to)11622-11630
Number of pages9
JournalJournal of the American Chemical Society
Volume137
Issue number36
DOIs
StatePublished - Sep 16 2015

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Proteins
Secondary Protein Structure
Modulators
Conformations
Databases
Modulation
Research

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Protein-Protein Interactions Mediated by Helical Tertiary Structure Motifs. / Watkins, Andrew M.; Wuo, Michael G.; Arora, Paramjit.

In: Journal of the American Chemical Society, Vol. 137, No. 36, 16.09.2015, p. 11622-11630.

Research output: Contribution to journalArticle

Watkins, Andrew M. ; Wuo, Michael G. ; Arora, Paramjit. / Protein-Protein Interactions Mediated by Helical Tertiary Structure Motifs. In: Journal of the American Chemical Society. 2015 ; Vol. 137, No. 36. pp. 11622-11630.
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