Structure and function of multiple Ca^sup 2+^-binding sites in a K+ channel regulator of K+ conductance (RCK) domain

• Published in: Proceedings of the National Academy of Sciences - PNAS 2011-10, Vol.108 (43), p.17684
• Main Authors: Pau, Victor P T, Smith, Frank J, Taylor, Alexander B, Parfenova, Liubov V, Samakai, Elsie, Callaghan, Matthew M, Abarca-Heidemann, Karin, Hart, P John, Rothberg, Brad S
• Format: Article
• Language: English
• Subjects: Binding sites; Blood pressure; Calcium; Crystallography; Neurons
• ISSN: 0027-8424; 1091-6490

Regulator of K+ conductance (RCK) domains control the activity of a variety of K+ transporters and channels, including the human large conductance Ca...-activated K+ channel that is important for blood pressure regulation and control of neuronal firing, and MthK, a prokaryotic Ca...-gated K+ channel that has yielded structural insight toward mechanisms of RCK domain-controlled channel gating. In MthK, a gating ring of eight RCK domains regulates channel activation by Ca... Here, using electrophysiology and X-ray crystallography, we show that each RCK domain contributes to three different regulatory Ca...-binding sites, two of which are located at the interfaces between adjacent RCK domains. The additional Ca...-binding sites, resulting in a stoichiometry of 24 Ca... ions per channel, is consistent with the steep relation between [Ca...] and MthK channel activity. Comparison of Ca...-bound and unliganded RCK domains suggests a physical mechanism for Ca...-dependent conformational changes that underlie gating in this class of channels. (ProQuest: ... denotes formulae/symbols omitted.)