Three-dimensional structure of the gap junction connexon.
The gap junction membrane channel is composed of macular aggregations of intercellular channels permitting the direct intercellular transfer of ions and small molecules. Each intercellular channel is formed by the apposition of two hexameric transmembrane channels (connexons), one from each cell. The interlocking of the two channels occurs extracellularly in a narrow 2.5-nm "gap" separating the junctional membranes. The channel-channel interaction is known to be selective between members of the family of proteins, called connexins, which oligomerize into the connexons. In addition to selectivity, the molecular interfaces involved in the extracellular interactions between connexons must be very congruent, since the intercellular channel must provide high resistances to the leakage of small ions between the channel lumen and the extracellular space. By using a recently developed biochemical procedure for obtaining ordered arrays of connexons from gap junctions split in the extracellular gap, (Ghoshroy, S., D. A. Goodenough, and G. E. Sosinsky. 1994. Preparation, characterization, and structure of half gap junctional layers spit with urea and EGTA. J. Membr. Biol. 146:15-28) a three-dimensional reconstruction of a connexon has been obtained by electron crystallographic methods. This reconstruction emphasizes the structural asymmetry between the extracellular and cytoplasmic domains and assigns lobed structural features to the extracellular domains of the connexon. The implication of our hemichannel structure is discussed in relation to the in vivo state of unpaired connexons, which have been shown to exist in the plasma membrane.
Perkins
G
G
Department of Neurosciences, University of California, San Diego, La Jolla 92093-0322, USA. perkins@ncmir.ucsd.edu
Goodenough
D
D
Sosinsky
G
G
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000648:ultrastructure; D003196:Computer Graphics; D017630:Connexins / Q000737:chemistry*; D017629:Gap Junctions / Q000737:chemistry* / Q000648:ultrastructure; D007091:Image Processing, Computer-Assisted; D007473:Ion Channels / Q000737:chemistry*; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry; D008854:Microscopy, Electron; D008958:Models, Molecular; D051381:Rats
D017630:Connexins; D007473:Ion Channels; D008565:Membrane Proteins