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-Structure paper
タイトル | Structure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 3821, Year 2023 |
掲載日 | 2023年6月28日 |
著者 | Johanna L Syrjänen / Max Epstein / Ricardo Gómez / Hiro Furukawa / |
PubMed 要旨 | Calcium homeostasis modulator 1 (CALHM1) is a voltage-dependent channel involved in neuromodulation and gustatory signaling. Despite recent progress in the structural biology of CALHM1, insights into ...Calcium homeostasis modulator 1 (CALHM1) is a voltage-dependent channel involved in neuromodulation and gustatory signaling. Despite recent progress in the structural biology of CALHM1, insights into functional regulation, pore architecture, and channel blockade remain limited. Here we present the cryo-EM structure of human CALHM1, revealing an octameric assembly pattern similar to the non-mammalian CALHM1s and the lipid-binding pocket conserved across species. We demonstrate by MD simulations that this pocket preferentially binds a phospholipid over cholesterol to stabilize its structure and regulate the channel activities. Finally, we show that residues in the amino-terminal helix form the channel pore that ruthenium red binds and blocks. |
リンク | Nat Commun / PubMed:37380652 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.8 - 4.73 Å |
構造データ | EMDB-40229, PDB-8gmp: EMDB-40230, PDB-8gmq: EMDB-40231, PDB-8gmr: EMDB-40232, PDB-8s8z: EMDB-40233, PDB-8s90: |
化合物 | ChemComp-POV: ChemComp-R2R: |
由来 |
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キーワード | MEMBRANE PROTEIN / taste / assembly / calcium homeostasis modulator protein / channel / lipid binding / large-pore channel / ruthenium red |