The connexins are a family of transmembrane proteins (21 isoforms in human) that form intercellular channels for cell-to-cell communication 1, 2. These results illustrate how the aqueous-lipid environment is integrated with the architectural stability, structure and function of gap junction communication channels. In addition, ~400 water molecules are resolved in the CryoEM map, localized throughout the intercellular permeation pathway and contributing to the channel architecture. 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. Structural characterization by CryoEM reveals a lipid-induced stabilization to the channel, resulting in a 3D reconstruction at 1.9 Å resolution. Here, we incorporate native connexin-46/50 (Cx46/50) intercellular channels into a dual lipid nanodisc system, mimicking a native cell-to-cell junction.

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. Gap junctions establish direct pathways for cells to transfer metabolic and electrical messages.

Janetter delete dm