5TWV

Cryo-EM structure of the pancreatic ATP-sensitive K+ channel SUR1/Kir6.2 in the presence of ATP and glibenclamide

5TWV の概要

• エントリーDOI: 10.2210/pdb5twv/pdb
• EMDBエントリー: 8470
• 分子名称: ATP-sensitive inward rectifier potassium channel 11, ATP-binding cassette sub-family C member 8, ADENOSINE-5'-TRIPHOSPHATE (3 entities in total)
• 機能のキーワード: katp, kir6.2, sur1, potassium channel, transport protein
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 889933.66

構造登録者

Martin, G.M.,Yoshioka, C.,Chen, J.Z.,Shyng, S.L. (登録日: 2016-11-14, 公開日: 2017-01-25, 最終更新日: 2024-10-23)

主引用文献

Martin, G.M.,Yoshioka, C.,Rex, E.A.,Fay, J.F.,Xie, Q.,Whorton, M.R.,Chen, J.Z.,Shyng, S.L.
Cryo-EM structure of the ATP-sensitive potassium channel illuminates mechanisms of assembly and gating.
Elife, 6:-, 2017

PubMed Abstract: K channels are metabolic sensors that couple cell energetics to membrane excitability. In pancreatic β-cells, channels formed by SUR1 and Kir6.2 regulate insulin secretion and are the targets of antidiabetic sulfonylureas. Here, we used cryo-EM to elucidate structural basis of channel assembly and gating. The structure, determined in the presence of ATP and the sulfonylurea glibenclamide, at ~6 Å resolution reveals a closed Kir6.2 tetrameric core with four peripheral SUR1s each anchored to a Kir6.2 by its N-terminal transmembrane domain (TMD0). Intricate interactions between TMD0, the loop following TMD0, and Kir6.2 near the proposed PIP binding site, and where ATP density is observed, suggest SUR1 may contribute to ATP and PIP binding to enhance Kir6.2 sensitivity to both. The SUR1-ABC core is found in an unusual inward-facing conformation whereby the two nucleotide binding domains are misaligned along a two-fold symmetry axis, revealing a possible mechanism by which glibenclamide inhibits channel activity.

PubMed: 28092267
DOI: 10.7554/eLife.24149

実験手法

ELECTRON MICROSCOPY (6.3 Å)