6PQQ

Cryo-EM structure of human TRPA1 C621S mutant in the apo state

6PQQ の概要

• エントリーDOI: 10.2210/pdb6pqq/pdb
• EMDBエントリー: 20449 20450 20451
• 分子名称: Transient receptor potential cation channel subfamily A member 1, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate (3 entities in total)
• 機能のキーワード: ion channel, trp channel, trpa channel, trpa1 channel, irritant sensing, apo state, membrane protein, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 546358.46

構造登録者

Suo, Y.,Wang, Z.,Zubcevic, L.,Hsu, A.L.,He, Q.,Borgnia, M.J.,Ji, R.-R.,Lee, S.-Y. (登録日: 2019-07-09, 公開日: 2020-01-08, 最終更新日: 2024-03-20)

主引用文献

Suo, Y.,Wang, Z.,Zubcevic, L.,Hsu, A.L.,He, Q.,Borgnia, M.J.,Ji, R.R.,Lee, S.Y.
Structural Insights into Electrophile Irritant Sensing by the Human TRPA1 Channel.
Neuron, 105:882-, 2020

PubMed Abstract: Transient receptor potential channel subfamily A member 1 (TRPA1) is a Ca-permeable cation channel that serves as one of the primary sensors of environmental irritants and noxious substances. Many TRPA1 agonists are electrophiles that are recognized by TRPA1 via covalent bond modifications of specific cysteine residues located in the cytoplasmic domains. However, a mechanistic understanding of electrophile sensing by TRPA1 has been limited due to a lack of high-resolution structural information. Here, we present the cryoelectron microscopy (cryo-EM) structures of nanodisc-reconstituted ligand-free TRPA1 and TRPA1 in complex with the covalent agonists JT010 and BITC at 2.8, 2.9, and 3.1 Å, respectively. Our structural and functional studies provide the molecular basis for electrophile recognition by the extraordinarily reactive C621 in TRPA1 and mechanistic insights into electrophile-dependent conformational changes in TRPA1. This work also provides a platform for future drug development targeting TRPA1.

PubMed: 31866091
DOI: 10.1016/j.neuron.2019.11.023

実験手法

ELECTRON MICROSCOPY (2.81 Å)