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TitleIn situ structure of the human gap junction.
Journal, issue, pagesSci Adv, Vol. 12, Issue 20, Page eaea4183, Year 2026
Publish dateMay 15, 2026
AuthorsEvans Eshriew / Esa-Pekka Kumpula / Shiv K Sah-Teli / Amiel Abettan / Amina Djurabekova / Vivek Sharma / Juha T Huiskonen /
PubMed AbstractGap junction plaques (GJPs) enable direct intercellular communication and consist of connexin channels arranged into two-dimensional lattices. While structures of purified connexin channels have ...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.
External linksSci Adv / PubMed:42127184 / PubMed Central
MethodsEM (subtomogram averaging) / EM (tomography)
Resolution14.0 Å
Structure data

54024

9rkx

EMDB-54024: In situ structure of the human Cx43 gap junction
PDB-9rkx: Atomic model of Cx43 gap junction channel rigid-body fitted to the in situ structure of the human Cx43 gap junction
Method: EM (subtomogram averaging) / Resolution: 14.0 Å

EMDB-54025: Tomogram of human connexin43 / GJC gap junction plaque
Method: EM (tomography)

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Cx43 / GJC / gap junction / cell signalling

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