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1: Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19813-8. Epub 2007 Dec 5.
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Principles underlying energetic coupling along an allosteric communication trajectory of a voltage-activated K+ channel.

Sadovsky E, Yifrach O.

Department of Life Sciences and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.

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 voltage-gated 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.

Publication Types:
PMID: 18077413 [PubMed - indexed for MEDLINE]

PMCID: PMC2148381