8gmq

Publication Abstract from PubMed

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.

Structure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red.,Syrjanen JL, Epstein M, Gomez R, Furukawa H Nat Commun. 2023 Jun 28;14(1):3821. doi: 10.1038/s41467-023-39388-3. PMID:37380652^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.