Physical Determinants of Strong Voltage Sensitivity of K+ Channel Block

Journal Article · Thu Jan 01 04:00:00 EST 2009 · Nature Structural and Molecular Biology

DOI:https://doi.org/10.1038/nsmb.1717· OSTI ID:1019657

Xu, Y; Shin, H; Szep, S; Lu, Z

Strong voltage sensitivity of inward-rectifier K{sup +} (Kir) channels has been hypothesized to arise primarily from an intracellular blocker displacing up to five K{sup +} ions from the wide, intracellular part of the ion conduction pore outwardly across the narrow ion-selectivity filter. The validity of this hypothesis depends on two assumptions: (i) that five ion sites are located intracellular to the filter and (ii) that the blocker can force essentially unidirectional K{sup +} movement in a pore region generally wider than the combined dimensions of the blocker plus a K{sup +} ion. Here we present a crystal structure of the cytoplasmic portion of a Kir channel with five ions bound and demonstrate that a constriction near the intracellular end of the pore, acting as a gasket, prevents K{sup +} ions from bypassing the blocker. This heretofore unrecognized 'gasket' ensures that the blocker can effectively displace K{sup +} ions across the selectivity filter to generate exceedingly strong voltage sensitivity.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: DOE - OFFICE OF SCIENCE
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 1019657
• Report Number(s): BNL--95741-2011-JA
• Journal Information: Nature Structural and Molecular Biology, Journal Name: Nature Structural and Molecular Biology Journal Issue: 12 Vol. 16; ISSN 1545-9993
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
CRYSTAL STRUCTURE
DIMENSIONS
HYPOTHESIS
SENSITIVITY
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