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-Structure paper
| タイトル | Structural dynamics and permeability of the TRPV3 pentamer. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 16, Issue 1, Page 4520, Year 2025 |
| 掲載日 | 2025年5月15日 |
著者 | Shifra Lansky / Zhaokun Wang / Oliver B Clarke / Christophe Chipot / Simon Scheuring / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:40374654 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 4.07 Å |
| 構造データ | EMDB-46907, PDB-9dij: |
| 由来 |
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キーワード | MEMBRANE PROTEIN / Ion channel / transient receptor potential channel / alternative oligomeric state / pore dilation |
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