Crystal Structures of a Ligand-free MthK Gating Ring: Insights into the Ligand Gating Mechanism of K.sup.+ Channels

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2006.08.029 Byline: Sheng Ye (1), Yang Li (1), Liping Chen (1), Youxing Jiang (1) Abstract: MthK is a prokaryotic Ca.sup.2+-gated K.sup.+ channel that, like other ligand-gated channels, converts the chemical energy of ligand binding to the mechanical force of channel opening. The channel's eight ligand-binding domains, the RCK domains, form an octameric gating ring in which Ca.sup.2+ binding induces conformational changes that open the channel. Here we present the crystal structures of the MthK gating ring in closed and partially open states at 2.8 A, both obtained from the same crystal grown in the absence of Ca.sup.2+. Furthermore, our biochemical and electrophysiological analyses demonstrate that MthK is regulated by both Ca.sup.2+ and pH. Ca.sup.2+ regulates the channel by changing the equilibrium of the gating ring between closed and open states, while pH regulates channel gating by affecting gating-ring stability. Our findings, along with the previously determined open MthK structure, allow us to elucidate the ligand gating mechanism of RCK-regulated K.sup.+ channels. Author Affiliation: (1) Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA Article History: Received 16 February 2006; Revised 8 May 2006; Accepted 11 August 2006 Article Note: (miscellaneous) Published: September 21, 2006