Principles underlying energetic coupling along an allosteric communication trajectory of a voltage-activated K+ channel

Evgeniya Sadovsky, Ofer Yifrach

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

The information flow between distal elements of a protein may rely on allosteric communication trajectories lying along the protein's tertiary or quaternary structure. To unravel the underlying features of energy parsing along allosteric pathways in voltagegated K+ channels, high-order thermodynamic coupling analysis was performed. We report that such allosteric trajectories are functionally conserved and delineated by well defined boundaries. Moreover, allosteric trajectories assume a hierarchical organization whereby increasingly stronger layers of cooperative residue interactions act to ensure efficient and cooperative long-range coupling between distal channel regions. Such long-range communication is brought about by a coupling of local and global conformational changes, suggesting that the allosteric trajectory also corresponds to a pathway of physical deformation. Supported by theoretical analyses and analogy to studies analyzing the contribution of long-range residue coupling to protein stability, we propose that such experimentally derived trajectory features are a general property of allosterically regulated proteins.

Original languageEnglish
Pages (from-to)19813-19818
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number50
DOIs
StatePublished - 11 Dec 2007

Keywords

  • Conformational changes
  • Cooperativity
  • Double-mutant cycles
  • Hill coefficient
  • Nonadditivity

ASJC Scopus subject areas

  • General

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