“From Plaques to Pores: In Situ Architecture and Isoform-Specific Gating of Human Gap Junction Channels”
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Date and Time
4:00 PM – 5:30 PM Thursday, January 22th, 2026
Location
Hybrid（CryoEM building and Zoom）
Speaker
Juha Huiskonen
Professor of Structural Biology, University of Helsinki
Director of the Institute of Biotechnology (HiLIFE – Helsinki Institute of Life Science)
Member of the Molecular and Integrative Biosciences Research Programme
Head of the Laboratory of Structural Biology at the Institute of Biotechnology
Abstract
Gap junction channels formed by connexins underpin electrical and biochemical coupling across tissues, yet the structural principles that govern their assembly and gating remain only partially defined. I will present two complementary structural studies that bridge native-membrane organization with atomic-level mechanisms of channel function. Our in situ cryo-ET structure of human Cx43 gap junction plaques at 14 Å reveals how the extensive C-terminal domain mediates lateral channel interactions critical for plaque formation. Supported by molecular simulations, we identify lipid and cholesterol densities between channels, resolving long-standing questions about the molecular determinants of gap junction lattice organization. In parallel, cryo-EM structures of human Cx45 in apo and Ca²⁺-bound forms at near-atomic resolution describe a compact and uniquely shaped pore, distinct N-terminal conformations, and C-terminal–intracellular loop interactions that define an isoform-specific gating mechanism. Ca²⁺ binding stabilizes a new conformation of E41 without inducing global motion, highlighting a subtle regulatory mechanism consistent with a semi-closed state.
Together, these findings contribute to an integrated view of connexin biology, revealing how structural diversity across isoforms and spatial organization within plaques contribute to tissue-specific modes of intercellular communication.