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Structure of the MthK RCK in complex with cadmium.

Abstract：

:RCK is a cytoplasmic regulatory domain of calcium-gated potassium channels. Binding of Ca(2+) by RCK leads to channel activation through a series of yet unknown conformational changes. Structures of the K(+) channel, MthK, and its cytoplasmic RCK domain revealed two binding sites for Ca(2+) per dimer. We determined the crystal structure of RCK in complex with Cd(2+) at 2.2A resolution. Cd(2+) activates MthK more efficiently, and binds at the same binding sites for Ca(2+) but with reduced coordination number. Two additional binding sites for Cd(2+) are found per dimer; one on the main Rossman-fold lobe, and the other on the small lobe of RCK. Using patch-clamp experiments, we demonstrate that Cd(2+) binding to these novel sites enhances activation by Cd(2+) and not by Ca(2+). The structure reveals a large negatively charged surface patch in the proximity of the Ca(2+)/Cd(2+) binding sites, charge neutralization of which appears to promote the channel open state.

journal_name

J Struct Biol

journal_title

Journal of structural biology

authors

Dvir H,Valera E,Choe S

doi

10.1016/j.jsb.2010.03.020

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

231-7

issue

2

eissn

1047-8477

issn

1095-8657

pii

S1047-8477(10)00097-3

journal_volume

171

pub_type

杂志文章

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