7Y1K

Structure of SUR2A in complex with Mg-ATP, Mg-ADP and repaglinide in the inward-facing conformation

7Y1K の概要

• エントリーDOI: 10.2210/pdb7y1k/pdb
• EMDBエントリー: 33564
• 分子名称: ATP-binding cassette sub-family C member 9, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: sur2a, abc transporter, repaglinide, 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: 175736.00

構造登録者

Chen, L.,Ding, D.,Hou, T. (登録日: 2022-06-08, 公開日: 2023-06-14, 最終更新日: 2023-10-11)

主引用文献

Ding, D.,Hou, T.,Wei, M.,Wu, J.X.,Chen, L.
The inhibition mechanism of the SUR2A-containing K ATP channel by a regulatory helix.
Nat Commun, 14:3608-3608, 2023

PubMed Abstract: K channels are metabolic sensors for intracellular ATP/ADP ratios, play essential roles in many physiological processes, and are implicated in a spectrum of pathological conditions. SUR2A-containing K channels differ from other subtypes in their sensitivity to Mg-ADP activation. However, the underlying structural mechanism remains poorly understood. Here we present a series of cryo-EM structures of SUR2A in the presence of different combinations of Mg-nucleotides and the allosteric inhibitor repaglinide. These structures uncover regulatory helix (R helix) on the NBD1-TMD2 linker, which wedges between NBD1 and NBD2. R helix stabilizes SUR2A in the NBD-separated conformation to inhibit channel activation. The competitive binding of Mg-ADP with Mg-ATP to NBD2 mobilizes the R helix to relieve such inhibition, allowing channel activation. The structures of SUR2B in similar conditions suggest that the C-terminal 42 residues of SUR2B enhance the structural dynamics of NBD2 and facilitate the dissociation of the R helix and the binding of Mg-ADP to NBD2, promoting NBD dimerization and subsequent channel activation.

PubMed: 37330603
DOI: 10.1038/s41467-023-39379-4

実験手法

ELECTRON MICROSCOPY (3.8 Å)