The structures and gating mechanism of human calcium homeostasis modulator 2.

ABSTRACT: Calcium homeostasis modulators (CALHMs) are voltage-gated, Ca²⁺-inhibited nonselective ion channels that act as major ATP release channels, and have important roles in gustatory signalling and neuronal toxicity^1-3. Dysfunction of CALHMs has previously been linked to neurological disorders¹. Here we present cryo-electron microscopy structures of the human CALHM2 channel in the Ca²⁺-free active or open state and in the ruthenium red (RUR)-bound inhibited state, at resolutions up to 2.7 Å. Our work shows that purified CALHM2 channels form both gap junctions and undecameric hemichannels. The protomer shows a mirrored arrangement of the transmembrane domains (helices S1-S4) relative to other channels with a similar topology, such as connexins, innexin

SUBMITTER: Choi W 

PROVIDER: S-EPMC8018591 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature