Chapter 1: Gap Junction Structure: New Structures and New Insights

Abstract

Gap junctions among tissue cells play an essential role in the passage of molecules from the cytoplasm of one cell to its neighbor. Gap junction channels can be isolated as two-dimensional crystals containing hexagonally packed membrane channels, individual channels, or individual hemichannels. Electron microscopy and X-ray diffraction have been used to characterize these structures since the first discovery by electron microscopy of these cell–cell contacts in the 1960s. The gap junction membrane channel consists of two hexameric oligomers. The gap junction proteins are a multigene family with a specific folding topology and oligomerize to form distinct macromolecular structures. The “Holy Grail” of the molecular structure determination is the organization of the atoms of the intercellular channels in these maculae. Although this goal seems unachievable, new and independently determined gap junction structures at higher resolutions have helped to elucidate the secondary structural organization of the connexins. Simultaneously, site directed mutagenesis and chimeras of the connexins have provided information about structure through data on loss, gain, or change in function. This chapter presents these new structures in the context of the earlier structural models that were based on previous structures obtained from electron microscopy, X-ray diffraction, and genetic manipulation of the protein. In particular, this chapter discusses the arrangement of α -helical and β sheet components in the gap junction membrane channel and their functional role in the cytoplasmic, transmembrane, and extracellular domains of the connexin oligomer, the connexon.