Gap junction hemichannels are membrane-embedded proteins that, when joined at their extracellular faces, enable small molecules (such as ions, peptides, or second messengers) to pass directly between adjacent cells. The permeability of the hemichannel can be modulated by conformational changes, and mutations in connexin26 are associated with human diseases. Oshima et al. have determined the electron crystallographic structure, at a resolution of 10 to 14 Å, of a mutant connexin26 protein related to the one linked to hereditary deafness. The electron density map revealed that the purified hemichannels had apparently reassociated to form a complete channel. Both the mutated connexin used and the conditions for crystallization would have favored a closed conformation, and a prominent density right in the center of the pore was observed. The authors propose that this plug is likely formed from the 20-residue N-terminal tail of connexin. Such a plug would allow the conductance of each hemichannel to be modulated independently; the plugs on both sides would need to be ejected in order to create a fully open channel. — LBR
Proc. Natl. Acad. Sci. U.S.A. 104, 10034 (2007).