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Publication Abstract from PubMed

RCK domains control activity of a variety of K(+) channels and transporters through binding of cytoplasmic ligands. To gain insight toward mechanisms of RCK domain activation, we solved the structure of the RCK domain from the Ca(2+)-gated K(+) channel, MthK, bound with Ba(2+), at 3.1 A resolution. The Ba(2+)-bound RCK domain was assembled as an octameric gating ring, as observed in structures of the full-length MthK channel, and shows Ba(2+) bound at several positions. One of the Ba(2+) sites, termed C1, overlaps with a known Ca(2+)-activation site, determined by residues D184 and E210. Functionally, Ba(2+) can activate reconstituted MthK channels as observed in electrophysiological recordings, whereas Mg(2+) (up to 100 mM) was ineffective. Ba(2+) activation was abolished by the mutation D184N, suggesting that Ba(2+) activates primarily through the C1 site. Our results suggest a working hypothesis for a sequence of ligand-dependent conformational changes that may underlie RCK domain activation and channel gating.

Crystal Structure of a Ba(2+)-Bound Gating Ring Reveals Elementary Steps in RCK Domain Activation.,Smith FJ, Pau VP, Cingolani G, Rothberg BS Structure. 2012 Dec 5;20(12):2038-47. doi: 10.1016/j.str.2012.09.014. Epub 2012, Oct 18. PMID:23085076^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.