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Published on: July 16, 2013
Lipids intercalate and mediate multi-channel assemblies of connexin-46/50 gap junctions
Connor S Garrels1,2, Janette B Myers1,2,3, Samson A Souza1,2
1Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR 97239, USA.
Biorxiv : the Preprint Server for Biology
|June 12, 2026
Summary
Lipid molecules, not proteins, organize gap junction channels into plaques. This lipid mediation influences channel function and provides new insights into cellular communication.
Area of Science:
- Structural biology
- Cellular biophysics
- Membrane protein complexes
Background:
- Gap junction channels facilitate intercellular communication.
- The structural organization of gap junction plaques remains poorly understood.
- Plaque formation influences junctional conductance.
Purpose of the Study:
- To elucidate the structural basis of gap junction channel organization within a membrane environment.
- To investigate the role of lipids in mediating channel-channel interactions in gap junction plaques.
- To determine high-resolution structures of connexin-46/50 (Cx46/50) channel assemblies.
Main Methods:
- Reconstitution of native lens Cx46/50 gap junction channels into MSP-based lipid nanodiscs.
- Single-particle cryo-electron microscopy (cryo-EM) for high-resolution structure determination.
- Refinement of single-channel structure to 1.8 Å resolution.
Main Results:
- Dual-channel assemblies revealed no ordered protein-protein contacts between channels.
- Ordered lipid density occupied the inter-channel space, indicating lipid-mediated packing.
- Specific lipid populations were stabilized at channel interfaces, interacting near the N-terminal gating domain.
- High-resolution structure revealed detailed chemical features of the Cx46/50 pore in the open state.
Conclusions:
- Lipids, not proteins, mediate the organization of Cx46/50 channels in plaque-like assemblies.
- Lipid-mediated channel packing influences the stabilization of specific lipid populations near the pore.
- These findings provide principles for lipid-mediated multi-channel organization and suggest mechanisms for tuning gap junction function through lipid interactions.
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