Calcium induced N-terminal gating and pore collapse in connexin-46/50 gap junctions.

ABSTRACT: Gap junctions facilitate electrical and metabolic coupling essential for tissue function. Under ischemic conditions (e.g., heart attack or stroke), elevated intracellular calcium (Ca²⁺) levels uncouple these cell-to-cell communication pathways to protect healthy cells from cytotoxic signals. Using single-particle cryo-EM, we elucidate details of the Ca²⁺-induced gating mechanism of native connexin-46/50 (Cx46/50) gap junctions. The resolved structures reveal Ca²⁺ binding sites within the channel pore that alter the chemical environment of the permeation pathway and induce diverse occluded and gated states through N-terminal domain remodeling. Moreover, subunit rearrangements lead to pore collapse, enabling steric blockade by the N-terminal domains, r

SUBMITTER: Flores JA 

PROVIDER: S-EPMC11844560 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature