6UVR

Human Connexin-26 (Neutral pH open conformation)

Summary for 6UVR

• Entry DOI: 10.2210/pdb6uvr/pdb
• Related: 6UVS 6UVT
• EMDB information: 20914 20915 20916
• Descriptor: Gap junction beta-2 protein (1 entity in total)
• Functional Keywords: gap junction channel, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 12
• Total formula weight: 314579.34

Authors

Khan, A.K.,Jagielnicki, M.,Purdy, M.D.,Yeager, M. (deposition date: 2019-11-04, release date: 2020-04-29, Last modification date: 2024-11-06)

Primary citation

Khan, A.K.,Jagielnicki, M.,McIntire, W.E.,Purdy, M.D.,Dharmarajan, V.,Griffin, P.R.,Yeager, M.
A Steric "Ball-and-Chain" Mechanism for pH-Mediated Regulation of Gap Junction Channels.
Cell Rep, 31:107482-107482, 2020

PubMed Abstract: Gap junction channels (GJCs) mediate intercellular communication and are gated by numerous conditions such as pH. The electron cryomicroscopy (cryo-EM) structure of Cx26 GJC at physiological pH recapitulates previous GJC structures in lipid bilayers. At pH 6.4, we identify two conformational states, one resembling the open physiological-pH structure and a closed conformation that displays six threads of density, that join to form a pore-occluding density. Crosslinking and hydrogen-deuterium exchange mass spectrometry reveal closer association between the N-terminal (NT) domains and the cytoplasmic loops (CL) at acidic pH. Previous electrophysiologic studies suggest an association between NT residue N14 and H100 near M2, which may trigger the observed movement of M2 toward M1 in our cryo-EM maps, thereby accounting for additional NT-CL crosslinks at acidic pH. We propose that these pH-induced interactions and conformational changes result in extension, ordering, and association of the acetylated NT domains to form a hexameric "ball-and-chain" gating particle.

PubMed: 32320665
DOI: 10.1016/j.celrep.2020.03.046

Experimental method

ELECTRON MICROSCOPY (4 Å)