7VLS

Structure of SUR2B in complex with MgATP/ADP and P1075

7VLS の概要

• エントリーDOI: 10.2210/pdb7vls/pdb
• EMDBエントリー: 32025
• 分子名称: Isoform SUR2B of ATP-binding cassette sub-family C member 9, CHOLESTEROL HEMISUCCINATE, ADENOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: sur2b, abc transporter, p1075, membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 176189.58

構造登録者

Chen, L.,Ding, D. (登録日: 2021-10-05, 公開日: 2022-05-18, 最終更新日: 2024-06-19)

主引用文献

Ding, D.,Wu, J.X.,Duan, X.,Ma, S.,Lai, L.,Chen, L.
Structural identification of vasodilator binding sites on the SUR2 subunit.
Nat Commun, 13:2675-2675, 2022

PubMed Abstract: ATP-sensitive potassium channels (K), composed of Kir6 and SUR subunits, convert the metabolic status of the cell into electrical signals. Pharmacological activation of SUR2- containing K channels by class of small molecule drugs known as K openers leads to hyperpolarization of excitable cells and to vasodilation. Thus, K openers could be used to treat cardiovascular diseases. However, where these vasodilators bind to K and how they activate the channel remains elusive. Here, we present cryo-EM structures of SUR2A and SUR2B subunits in complex with Mg-nucleotides and P1075 or levcromakalim, two chemically distinct K openers that are specific to SUR2. Both P1075 and levcromakalim bind to a common site in the transmembrane domain (TMD) of the SUR2 subunit, which is between TMD1 and TMD2 and is embraced by TM10, TM11, TM12, TM14, and TM17. These K openers synergize with Mg-nucleotides to stabilize SUR2 in the NBD-dimerized occluded state to activate the channel.

PubMed: 35562524
DOI: 10.1038/s41467-022-30428-y

実験手法

ELECTRON MICROSCOPY (3.3 Å)