8WPM

Cryo-EM structure of the human TRPC1/C4 heteromer in complex with Pico145

8WPM の概要

• エントリーDOI: 10.2210/pdb8wpm/pdb
• EMDBエントリー: 37719
• 分子名称: Short transient receptor potential channel 1, Short transient receptor potential channel 4, 7-[(4-chlorophenyl)methyl]-3-methyl-1-(3-oxidanylpropyl)-8-[3-(trifluoromethyloxy)phenoxy]purine-2,6-dione, ... (5 entities in total)
• 機能のキーワード: transient receptor potential, metal transport
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 409643.47

構造登録者

Won, J.,Jeong, H.,Lee, H.H. (登録日: 2023-10-10, 公開日: 2024-10-16, 最終更新日: 2025-07-02)

主引用文献

Won, J.,Kim, J.,Kim, J.,Ko, J.,Park, C.H.,Jeong, B.,Lee, S.E.,Jeong, H.,Kim, S.H.,Park, H.,So, I.,Lee, H.H.
Cryo-EM structure of the heteromeric TRPC1/TRPC4 channel.
Nat.Struct.Mol.Biol., 32:326-338, 2025

PubMed Abstract: Transient receptor potential (TRP) ion channels have a crucial role as cellular sensors, mediating diverse physical and chemical stimuli. The formation of heteromeric structures expands the functionality of TRP channels; however, their molecular architecture remains largely unknown. Here we present the cryo-electron microscopy structures of the human TRPC1/TRPC4 heteromer in the apo and antagonist-bound states, both consisting of one TRPC1 subunit and three TRPC4 subunits. The heteromer structure reveals a distinct ion-conduction pathway, including an asymmetrically constricted selectivity filter and an asymmetric lower gate, primarily attributed to the incorporation of TRPC1. Through a structure-guided electrophysiological assay, we show that both the selectivity filter and the lower part of the S6 helix participate in deciding overall preference for permeating monovalent cations. Moreover, we reveal that the introduction of one lysine residue of TRPC1 into the tetrameric central cavity is enough to render one of the most important functional consequences of TRPC heteromerization: reduced calcium permeability. Our results establish a framework for addressing the structure-function relationship of the heteromeric TRP channels.

PubMed: 39478185
DOI: 10.1038/s41594-024-01408-1

実験手法

ELECTRON MICROSCOPY (3.43 Å)