+検索条件
-Structure paper
タイトル | Vascular K channel structural dynamics reveal regulatory mechanism by Mg-nucleotides. |
---|---|
ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 118, Issue 44, Year 2021 |
掲載日 | 2021年11月2日 |
著者 | Min Woo Sung / Zhongying Yang / Camden M Driggers / Bruce L Patton / Barmak Mostofian / John D Russo / Daniel M Zuckerman / Show-Ling Shyng / |
PubMed 要旨 | Vascular tone is dependent on smooth muscle K channels comprising pore-forming Kir6.1 and regulatory SUR2B subunits, in which mutations cause Cantú syndrome. Unique among K isoforms, they lack ...Vascular tone is dependent on smooth muscle K channels comprising pore-forming Kir6.1 and regulatory SUR2B subunits, in which mutations cause Cantú syndrome. Unique among K isoforms, they lack spontaneous activity and require Mg-nucleotides for activation. Structural mechanisms underlying these properties are unknown. Here, we determined cryogenic electron microscopy structures of vascular K channels bound to inhibitory ATP and glibenclamide, which differ informatively from similarly determined pancreatic K channel isoform (Kir6.2/SUR1). Unlike SUR1, SUR2B subunits adopt distinct rotational "propeller" and "quatrefoil" geometries surrounding their Kir6.1 core. The glutamate/aspartate-rich linker connecting the two halves of the SUR-ABC core is observed in a quatrefoil-like conformation. Molecular dynamics simulations reveal MgADP-dependent dynamic tripartite interactions between this linker, SUR2B, and Kir6.1. The structures captured implicate a progression of intermediate states between MgADP-free inactivated, and MgADP-bound activated conformations wherein the glutamate/aspartate-rich linker participates as mobile autoinhibitory domain, suggesting a conformational pathway toward K channel activation. |
リンク | Proc Natl Acad Sci U S A / PubMed:34711681 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.4 - 4.2 Å |
構造データ | EMDB-23864, PDB-7mit: EMDB-23880, PDB-7mjo: EMDB-23881, PDB-7mjp: EMDB-23882, PDB-7mjq: |
化合物 | ChemComp-K: ChemComp-ATP: ChemComp-POV: ChemComp-PTY: ChemComp-P5S: ChemComp-GBM: |
由来 |
|
キーワード | TRANSPORT PROTEIN / KATP / potassium channel / vascular |