Crystal structures of a ligand-free MthK gating ring: insights into the ligand gating mechanism of K+ channels.
MthK is a prokaryotic Ca(2+)-gated K(+) 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(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(2+). Furthermore, our biochemical and electrophysiological analyses demonstrate that MthK is regulated by both Ca(2+) and pH. Ca(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(+) channels.
Ye
Sheng
S
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Li
Yang
Y
Chen
Liping
L
Jiang
Youxing
Y
D000494:Allosteric Regulation / Q000502:physiology; D001419:Bacteria / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D019281:Dimerization; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008024:Ligands; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008958:Models, Molecular; D011188:Potassium / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D020836:Protein Structure, Quaternary / Q000502:physiology; D021122:Protein Subunits / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D008024:Ligands; D024681:Potassium Channels, Calcium-Activated; D021122:Protein Subunits; D011188:Potassium; D002118:Calcium