Protein recognition and selection through conformational and mutually induced fit

Qian Wang, Pengzhi Zhang, Laurel Hoffman, Swarnendu Tripathi, Dirar Homouz, Yin Liu, M. Neal Waxham, Margaret S. Cheung

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Protein-protein interactions drive most every biological process, but in many instances the domains mediating recognition are disordered. How specificity in binding is attained in the absence of defined structure contrasts with well-established experimental and theoretical work describing ligand binding to protein. The signaling protein calmodulin presents a unique opportunity to investigate mechanisms for target recognition given that it interacts with several hundred different targets. By advancing coarsegrained computer simulations and experimental techniques, mechanistic insights were gained in defining the pathways leading to recognition and in how target selectivity can be achieved at the molecular level. A model requiring mutually induced conformational changes in both calmodulin and target proteins was necessary and broadly informs how proteins can achieve both high affinity and high specificity.

Original languageBritish English
Pages (from-to)20545-20550
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number51
DOIs
StatePublished - 17 Dec 2013

Keywords

  • Calmodulin binding target
  • Coarse-grained molecular simulations
  • Conformational flexibility
  • Hydrophobic motif
  • Stopped-flow fluorescence techniques

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