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Biophysical Journal 72: 533-544 (1997)
© 1997 the Biophysical Society

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Three-Dimensional Structure of the Gap Junction Connexon

Guy Perkins *, Dan Goodenough # and Gina Sosinsky * §

Department of Neurosciences University of California, San Diego, La Jolla, California 92093-0322, USA
Department of Biology, University of California, San Diego, La Jolla, California 92093-0322, USA
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115 USA

ABSTRACT

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 3.5-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. 1995. Preparation, characterization, and structure of half gap junctional layers split 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.




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Copyright © 1997 by the Biophysical Society.