Conformational changes in the human Cx43/GJA1 gap junction channel visualized using cryo-EM

Hyuk-Joon Lee, Hyung Jin Cha, Hyeongseop Jeong, Seu-Na Lee, Chang-Won Lee, Minsoo Kim, Jejoong Yoo and Jae-Sung Woo ()
Additional contact information
Hyuk-Joon Lee: Korea University
Hyung Jin Cha: Korea University
Hyeongseop Jeong: Korea University
Seu-Na Lee: Korea University
Chang-Won Lee: Korea University
Minsoo Kim: Sungkyunkwan University
Jejoong Yoo: Sungkyunkwan University
Jae-Sung Woo: Korea University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Connexin family proteins assemble into hexameric hemichannels in the cell membrane. The hemichannels dock together between two adjacent membranes to form gap junction intercellular channels (GJIChs). We report the cryo-electron microscopy structures of Cx43 GJICh, revealing the dynamic equilibrium state of various channel conformations in detergents and lipid nanodiscs. We identify three different N-terminal helix conformations of Cx43—gate-covering (GCN), pore-lining (PLN), and flexible intermediate (FIN)—that are randomly distributed in purified GJICh particles. The conformational equilibrium shifts to GCN by cholesteryl hemisuccinates and to PLN by C-terminal truncations and at varying pH. While GJIChs that mainly comprise GCN protomers are occluded by lipids, those containing conformationally heterogeneous protomers show markedly different pore sizes. We observe an α-to-π-helix transition in the first transmembrane helix, which creates a side opening to the membrane in the FIN and PLN conformations. This study provides basic structural information to understand the mechanisms of action and regulation of Cx43 GJICh.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36593-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36593-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-36593-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().