Structure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red

Syrjänen, Johanna L, Epstein, Max, Gómez, Ricardo, Furukawa, Hiro (June 2023) Structure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red. Nature Communications, 14 (1). p. 3821. ISSN 2041-1723 (Public Dataset)

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URL: https://www.ncbi.nlm.nih.gov/pubmed/37380652

DOI: 10.1038/s41467-023-39388-3

Abstract

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.

Item Type:	Paper
Subjects:	organism description > animal organism description > animal > bird organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > calcium channel organism description > animal > bird > chicken organism description > animal > mammal > primates > hominids organism description > animal > mammal > primates > hominids > human organism description > animal > mammal organs, tissues, organelles, cell types and functions organism description > animal > mammal > primates organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions
CSHL Authors:	Epstein, Max Furukawa, Hiro Syrjanen, Johanna L. Gomez, Ricardo
Communities:	CSHL labs > Furukawa lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	28 June 2023
Date Deposited:	22 Sep 2023 14:03
Last Modified:	11 Jan 2024 14:30
PMCID:	PMC10307800
Related URLs:	Publisher
Dataset ID:	EMDB: 40230 EMDB: 40231 EMDB: 40232 EMDB: 40233 EMDB: 40229 PDB: 8GMQ PDB: 8GMR PDB: 8S8Z PDB: 8S90 PDB: 8GMP
URI:	https://repository.cshl.edu/id/eprint/40965

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