Principles of allosteric interactions in cell signaling

Ruth Nussinov, Chung Jung Tsai, Jin Liu

Research output: Contribution to journalReview article

69 Scopus citations

Abstract

Linking cell signaling events to the fundamental physicochemical basis of the conformational behavior of single molecules and ultimately to cellular function is a key challenge facing the life sciences. Here we outline the emerging principles of allosteric interactions in cell signaling, with emphasis on the following points. (1) Allosteric efficacy is not a function of the chemical composition of the allosteric pocket but reflects the extent of the population shift between the inactive and active states. That is, the allosteric effect is determined by the extent of preferred binding, not by the overall binding affinity. (2) Coupling between the allosteric and active sites does not decide the allosteric effect; however, it does define the propagation pathways, the allosteric binding sites, and key on-path residues. (3) Atoms of allosteric effectors can act as "driver" or "anchor" and create attractive "pulling" or repulsive "pushing" interactions. Deciphering, quantifying, and integrating the multiple co-occurring events present daunting challenges to our scientific community.

Original languageEnglish
Pages (from-to)17692-17701
Number of pages10
JournalJournal of the American Chemical Society
Volume136
Issue number51
DOIs
StatePublished - 24 Dec 2014

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