9DIJ

4 Angstrom structure of the human TRPV3 pentamer

9DIJ の概要

• エントリーDOI: 10.2210/pdb9dij/pdb
• 関連するPDBエントリー: 8GKG
• EMDBエントリー: 46907
• 分子名称: Transient receptor potential cation channel subfamily V member 3 (1 entity in total)
• 機能のキーワード: ion channel, transient receptor potential channel, alternative oligomeric state, pore dilation, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 463345.00

構造登録者

Lansky, S.,Clarke, O.B.,Scheuring, S. (登録日: 2024-09-05, 公開日: 2025-05-21, 最終更新日: 2025-05-28)

主引用文献

Lansky, S.,Wang, Z.,Clarke, O.B.,Chipot, C.,Scheuring, S.
Structural dynamics and permeability of the TRPV3 pentamer.
Nat Commun, 16:4520-4520, 2025

PubMed Abstract: TRPV3 belongs to the large superfamily of tetrameric transient receptor potential (TRP) ion channels. Recently, using high-speed atomic force microscopy (HS-AFM), we discovered a rare and transient pentameric state for TRPV3 that is in equilibrium with the tetrameric state, and, using cryo-EM, we solved a low-resolution structure of the TRPV3 pentamer, in which, however, many residues were unresolved. Here, we present a higher resolution and more complete structure of the pentamer, revealing a domain-swapped architecture, a collapsed vanilloid binding site, and a large pore. Molecular dynamics simulations and potential of mean force calculations of the pentamer establish high protein dynamics and permeability to large cations. Subunit interface analysis, together with thermal denaturation experiments, led us to propose a molecular mechanism of the tetramer-to-pentamer transition, backed experimentally by HS-AFM observations. Collectively, our data demonstrate that the TRPV3 pentamer is in a hyper-activated state with unique, highly permissive permeation properties.

PubMed: 40374654
DOI: 10.1038/s41467-025-59798-9

実験手法

ELECTRON MICROSCOPY (4.07 Å)