8SI4

Cryo-EM structure of TRPM7 N1098Q mutant in GDN detergent in open state

8SI4 の概要

• エントリーDOI: 10.2210/pdb8si4/pdb
• 関連するPDBエントリー: 8SI2 8SI3
• EMDBエントリー: 40496 40497 40498
• 分子名称: Transient receptor potential cation channel subfamily M member 7, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, CHOLESTEROL, ... (6 entities in total)
• 機能のキーワード: transient receptor potential m family member 7, trp, channel, trpm7, trp channels, membrane protein, magnesium channel, n1098q, open state
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 632856.23

構造登録者

Nadezhdin, K.D.,Neuberger, A.,Sobolevsky, A.I. (登録日: 2023-04-14, 公開日: 2023-05-17, 最終更新日: 2024-10-09)

主引用文献

Nadezhdin, K.D.,Correia, L.,Narangoda, C.,Patel, D.S.,Neuberger, A.,Gudermann, T.,Kurnikova, M.G.,Chubanov, V.,Sobolevsky, A.I.
Structural mechanisms of TRPM7 activation and inhibition.
Nat Commun, 14:2639-2639, 2023

PubMed Abstract: The transient receptor potential channel TRPM7 is a master regulator of the organismal balance of divalent cations that plays an essential role in embryonic development, immune responses, cell mobility, proliferation, and differentiation. TRPM7 is implicated in neuronal and cardiovascular disorders, tumor progression and has emerged as a new drug target. Here we use cryo-EM, functional analysis, and molecular dynamics simulations to uncover two distinct structural mechanisms of TRPM7 activation by a gain-of-function mutation and by the agonist naltriben, which show different conformational dynamics and domain involvement. We identify a binding site for highly potent and selective inhibitors and show that they act by stabilizing the TRPM7 closed state. The discovered structural mechanisms provide foundations for understanding the molecular basis of TRPM7 channelopathies and drug development.

PubMed: 37156763
DOI: 10.1038/s41467-023-38362-3

実験手法

ELECTRON MICROSCOPY (2.46 Å)