Gap Junctions

Hans Brinker Meets Gap Junctions

Science's STKE  19 Jun 2007:
Vol. 2007, Issue 391, pp. tw219
DOI: 10.1126/stke.3912007tw219

Gap junction channels allow communication between adjacent cells. Hemichannels formed from connexin proteins, one in each cell membrane, come together to allow small molecules, from ions to second messengers and peptides, to pass between cells. Conductance of the channels can be modulated, and mutations in connexin26 are associated with human diseases, including hereditary deafness. Oshima et al. solved the electron crystallographic structure of a mutant connexin26 protein similar to the one that causes the human hearing disorder. They obtained 2D crystals and combined images of them to obtain a 3D density map showing three membranes and two sets of symmetrically related intercellular channels at a resolution of 10 Å in the membrane plane and 14.1 Å perpendicular to the membrane plane. Most striking was a prominent density right in the center of the pore, essentially plugging the pore. Although the structures do not allow tracing of the plug to connect with the primary protein sequence, the authors suspect that the plug represents one of the protein termini, probably the N terminus. The mutant used and the conditions for crystallization should yield channels in a closed conformation. Such a plug would allow conductance of each hemichannel to be independently modulated, with a conducting pore formed only when both hemichannels had their plugs deflected to the cytoplasmic side.

A. Oshima, K. Tani, Y. Hiroaki, Y. Fujiyoshi, G. E. Sosinsky, Three-dimensional structure of a human connexin26 gap junction channel reveals a plug in the vestibule. Proc. Natl. Acad. Sci. U.S.A. 104, 10034-10039 (2007). [Abstract] [Full Text]