The Journal of General Physiology
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Published online
doi:10.1085/jgp.200809968
The Journal of General Physiology, Vol. 131, No. 6, 537-548
The Rockefeller University Press, 0022-1295 $30.00
© Liu et al.
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ARTICLE

 Position and Role of the BK Channel {alpha} Subunit S0 Helix Inferred from Disulfide Crosslinking



Guoxia Liu1, Sergey I. Zakharov1, Lin Yang1, Shi-Xian Deng2, Donald W. Landry2, Arthur Karlin3, and Steven O. Marx1,4

1 Division of Cardiology, Department of Medicine; 2 Division of Experimental Therapeutics, Department of Medicine; 3 Center for Molecular Recognition, Departments of Biochemistry, Physiology, and Neurology; 4 Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032

Correspondence to A. Karlin: ak12{at}columbia.edu; or S.O. Marx: sm460{at}columbia.edu

The position and role of the unique N-terminal transmembrane (TM) helix, S0, in large-conductance, voltage- and calcium-activated potassium (BK) channels are undetermined. From the extents of intra-subunit, endogenous disulfide bond formation between cysteines substituted for the residues just outside the membrane domain, we infer that the extracellular flank of S0 is surrounded on three sides by the extracellular flanks of TM helices S1 and S2 and the four-residue extracellular loop between S3 and S4. Eight different double cysteine–substituted alphas, each with one cysteine in the S0 flank and one in the S3–S4 loop, were at least 90% disulfide cross-linked. Two of these alphas formed channels in which 90% cross-linking had no effect on the V50 or on the activation and deactivation rate constants. This implies that the extracellular ends of S0, S3, and S4 are close in the resting state and move in concert during voltage sensor activation. The association of S0 with the gating charge bearing S3 and S4 could contribute to the considerably larger electrostatic energy required to activate the BK channel compared with typical voltage-gated potassium channels with six TM helices.

G. Liu and S.I. Zakharov contributed equally to this work.

Abbreviations used in this paper: BK, large-conductance, voltage- and calcium-activated potassium; HRV, human rhinovirus; PDI, protein disulfide isomerase; pWT, pseudo-wild-type; QPD, quaternary piperazinium diamide; TM, transmembrane; WT, wild-type.

© 2008 Liu et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jgp.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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