Structure and biochemistry of gap junctions

Abstract

Publisher Summary This chapter discusses the structure and biochemistry of gap junction. The conduit for intercellular communication is formed by connexons in register among closely apposed cells. Gap junction channels can be viewed as having a modular design. Homology in the transmembrane sequences suggests that the bundle of 24 α helices that form each connexon is likely be a common architecture for the transmembrane channel. Similarly, sequence homology in the extracellular domains suggests similar mechanisms for connexon–connexon interactions. The identification of specific functional sites or domains is critical for understanding the regulation of gap junction channels. Instead of blindly accumulating site mutations, a better strategy may be the generation of chimeric connexins where a loop domain of one connexin can be substituted for another. Currently, there are numerous areas for continued exploration of the structural and functional properties of gap junction channels—delineation of the precise interactions between different regions in the channel; the precise folding of the extracellular loops that confers stability but also specificity in connexon–connexon pairing; the identification and orientation of the transmembrane α helices in the 3D map; and specific mechanisms for gating. The regulation of gap junction channels is particularly fascinating as they manifest properties of both ligand-gated channels.