Year: 2026
Type: article
Abstract: ABSTRACT Gap junctions facilitate electrical and metabolic coupling essential for tissue function. Under ischemic conditions ( e.g., heart attack or stroke), elevated intracellular calcium (Ca 2+ ) 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 Ca 2+ -induced gating mechanism of native connexin-46/50 (Cx46/50) gap junctions. The resolved structures reveal Ca 2+ 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, reminiscent of the “iris model” of gating proposed over four decades ago. These findings unify and expand key elements of previous gating models, providing mechanistic insights into how Ca 2+ signaling regulates gap junction uncoupling and broader implications for understanding cell stress responses and tissue protection.
Source: Nature Communications
Language: English
Topic: Connexins and lens biology
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: Effect of lipid environment on the structure and organization of connexin-46/50 gap junction channels, High Performance Computing and Machine Learning Infrastructure for Oregon Life Sciences, Pacific Northwest Center for Cryo-EM, G9000373674, Dynamic Mechanisms of Membrane Channel Gating by CryoEM
OpenAlex ID: W7214090419