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Proc Natl Acad Sci U S A. 2007 May 29;104(22):9260-5. Epub 2007 May 22.

Selectivity in K+ channels is due to topological control of the permeant ion's coordinated state.

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1
Department of Molecular Biology and Center for Theoretical Biological Physics, The Scripps Research Institute, 10550 North Torrey Pines Road, TPC 6, La Jolla, CA 92037, USA.

Abstract

The selectivity filter of K+ channels provides specific coordinative interactions between dipolar carbonyl ligands, water, and the permeant cation, which allow for selective flow of K+ over (most importantly) Na+ across the cell membrane. Although a structural viewpoint attributes K+ selectivity to coordination geometry provided by the filter, recent molecular dynamics simulation studies attribute it to dynamic and unique chemical/electrostatic properties of the filter's carbonyl ligands. Here we provide a simple theoretical analysis of K+ and Na+ complexation with water in the context of simplified binding site models and bulk solution. Our analysis reveals that water molecules and carbonyl groups can both provide K+ selective environments if equivalent constraints are imposed on the coordination number of the complex. Absence of such constraints annihilates selectivity, demonstrating that whether a coordinating ligand is a water molecule or a carbonyl group, "external" or "topological" constraints/forces must be imposed on an ion-coordinated complex to elicit selective binding. These forces must inevitably originate from the channel protein, because in bulk water, which, by definition, presents a nonselective medium, the coordination number is allowed to relax to suit the ion. We show that the coordination geometry of K+ channel binding sites is replicated by 8-fold complexation of K+ in both water and simplified binding site models due to dominance of local interactions within a complex and is thus a requirement for topologically constraining the coordination number to a specific value.

PMID:
17519335
PMCID:
PMC1890482
DOI:
10.1073/pnas.0700554104
[Indexed for MEDLINE]
Free PMC Article
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