9RKX

Atomic model of Cx43 gap junction channel rigid-body fitted to the in situ structure of the human Cx43 gap junction

Summary for 9RKX

• Entry DOI: 10.2210/pdb9rkx/pdb
• EMDB information: 54024
• Descriptor: Gap junction alpha-1 protein (1 entity in total)
• Functional Keywords: cx43, gjc, gap junction, cell signalling, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 12
• Total formula weight: 516736.03

Authors

Eshriew, E.,Kumpula, E.-P.,Teli, S.,Huiskonen, J.T. (deposition date: 2025-06-15, release date: 2026-04-15, Last modification date: 2026-05-27)

Primary citation

Eshriew, E.,Kumpula, E.P.,Sah-Teli, S.K.,Abettan, A.,Djurabekova, A.,Sharma, V.,Huiskonen, J.T.
In situ structure of the human gap junction.
Sci Adv, 12:eaea4183-eaea4183, 2026

PubMed Abstract: Gap junction plaques (GJPs) enable direct intercellular communication and consist of connexin channels arranged into two-dimensional lattices. While structures of purified connexin channels have informed models of gating, they omit key intracellular regions and lack native context. Here, we use cryo-electron tomography and focused ion beam milling to determine the in situ structure of human connexin 43 (Cx43) GJPs in HEK293 cells at 14-Å resolution. We reveal a previously unresolved structural contribution of the large carboxyl-terminal domain to lateral channel-channel interactions that appear critical for plaque assembly. Coarse-grained molecular dynamics simulations suggest how lipids and cholesterol occupy the space between adjacent connexins. These findings resolve a decades-old question regarding gap junction organization and highlight a mechanistic function for the carboxyl-terminal domain, likely regulated by a helix-loop-helix motif. Our study provides a structural blueprint for understanding how connexin diversity and regulation shape tissue-level communication in health and disease.

PubMed: 42127184
DOI: 10.1126/sciadv.aea4183

Experimental method

ELECTRON MICROSCOPY (14 Å)