Potential of cryo-EM for high-resolution structural analysis of gap junction channels

Gap junction family proteins form conduits connecting the cytoplasm of adjacent cells, thereby enabling electrical and chemical coupling to maintain physiological homeostasis. Gap junction proteins comprise two gene families, connexins in chordates and innexins in pre-chordates. Their channel structures have been analyzed by electron or X-ray crystallography, but only a few atomic structures have been reported. Recent advances in single-particle cryo-electron microscopy (cryo-EM) will help to elucidate these structures further. Here the structural biology of gap junction channels utilizing crystallography and single-particle cryo-EM is overviewed to shed light on the functional mechanisms of cell-cell communication that are essential for multicellular organisms.