RT Journal Article
T1 Structure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red
A1 Syrjänen, Johanna L.
A1 Epstein, Max
A1 Gómez García, Ricardo
A1 Furukawa, Hiro
AB 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.
PB Nature Research
YR 2023
FD 2023-06-28
LK https://hdl.handle.net/20.500.14352/91777
UL https://hdl.handle.net/20.500.14352/91777
LA eng
NO Syrjänen, J.L., Epstein, M., Gómez, R. et al. Structure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red. Nat Commun 14, 3821 (2023). https://doi.org/10.1038/s41467-023-39388-3
NO Cold Spring Harbor Laboratory
NO Doug Fox Alzheimer
NO Robertson
NO Heartfelt Wing Alzheimer
DS Docta Complutense
RD 10 abr 2025