A Cα model for the transmembrane α helices of gap junction intercellular channels

Sarel J. Fleishman, Vinzenz M. Unger, Mark Yeager, Nir Ben-Tal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


Gap junction channels connect the cytoplasms of apposed cells via an intercellular conduit formed by the end-to-end docking of two hexameric hemichannels called connexons. We used electron cryomicroscopy to derive a three-dimensional density map at 5.7 Å in-plane and 19.8 Å vertical resolution, allowing us to identify the positions and tilt angles for the 24 α helices within each hemichannel. The four hydrophobic segments in connexin sequences were assigned to the α helices in the map based on biochemical and phylogenetic data. Analyses of evolutionary conservation and compensatory mutations in connexin evolution identified the packing interfaces between the helices. The final model, which specifies the coordinates of C α atoms in the transmembrane domain, provides a structural basis for understanding the different physiological effects of almost 30 mutations and polymorphisms in terms of structural deformations at the interfaces between helices, revealing an intimate connection between molecular structure and disease.

Original languageEnglish
Pages (from-to)879-888
Number of pages10
JournalMolecular Cell
Issue number6
StatePublished - 24 Sep 2004


FundersFunder number
Clore Israel Foundation
National Institutes of Health
National Heart, Lung, and Blood InstituteR01HL048908
Burroughs Wellcome Fund
American Heart Association
Israel Cancer Research Fund


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