Environmental Molecular Sciences Laboratory

A DOE Office of Science User Facility

This page lives in the old site. Check out our new site here.

Connexin-46/50 in a dynamic lipid environment resolved by CryoEM at 1.9?Å

Abstract: 

Gap junctions establish direct pathways for cells to transfer metabolic and electrical messages. The local lipid environment is known to affect the structure, stability and intercellular channel activity of gap junctions; however, the molecular basis for these effects remains unknown. Here, we incorporate native connexin-46/50 (Cx46/50) intercellular channels into a dual lipid nanodisc system, mimicking a native cell-to-cell junction. Structural characterization by CryoEM reveals a lipid-induced stabilization to the channel, resulting in a 3D reconstruction at 1.9?Å resolution. Together with all-atom molecular dynamics simulations, it is shown that Cx46/50 in turn imparts long-range stabilization to the dynamic local lipid environment that is specific to the extracellular lipid leaflet. In addition, ~400 water molecules are resolved in the CryoEM map, localized throughout the intercellular permeation pathway and contributing to the channel architecture. These results illustrate how the aqueous-lipid environment is integrated with the architectural stability, structure and function of gap junction communication channels.

Citation: 
Flores J., S.L. Reichow, J. Myers, C. Yoshioka, B. Haddad, J. Copperman, and D. Zuckerman. 2020. "Connexin-46/50 in a dynamic lipid environment resolved by CryoEM at 1.9?Å." <i>Nature Communications</i>. doi:10.1038/s41467-020-18120-5
Authors: 
Flores
Jonathan;Reichow
Steve L;Myers
Janette;Yoshioka
Craig;Haddad
Bassam;Copperman
Jeremy;Zuckerman
Daniel