7MJP

Vascular KATP channel: Kir6.1 SUR2B propeller-like conformation 2

7MJP の概要

• エントリーDOI: 10.2210/pdb7mjp/pdb
• EMDBエントリー: 23880 23881 23882
• 分子名称: ATP-sensitive inward rectifier potassium channel 8, Isoform SUR2B of ATP-binding cassette sub-family C member 9, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: katp, potassium channel, vascular, transport protein
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 370038.36

構造登録者

Sung, M.W.,Shyng, S.L. (登録日: 2021-04-20, 公開日: 2021-10-13, 最終更新日: 2024-05-29)

主引用文献

Sung, M.W.,Yang, Z.,Driggers, C.M.,Patton, B.L.,Mostofian, B.,Russo, J.D.,Zuckerman, D.M.,Shyng, S.L.
Vascular K ATP channel structural dynamics reveal regulatory mechanism by Mg-nucleotides.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: 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.

PubMed: 34711681
DOI: 10.1073/pnas.2109441118

実験手法

ELECTRON MICROSCOPY (4.2 Å)