Structural organization of intercellular channels II. Amino terminal domain of the connexins: sequence, functional roles, and structure.
The amino terminal domain (NT) of the connexins consists of their first 22-23 amino acids. Site-directed mutagenesis studies have demonstrated that NT amino acids are determinants of gap junction channel properties including unitary conductance, permeability/selectivity, and gating in response to transjunctional voltage. The importance of this region has also been emphasized by the identification of multiple disease-associated connexin mutants affecting amino acid residues in the NT region. The first part of the NT is α-helical. The structure of the Cx26 gap junction channel shows that the NT α-helix localizes within the channel, and lines the wall of the pore. Interactions of the amino acid residues in the NT with those in the transmembrane helices may be critical for holding the channel open. The predicted sites of these interactions and the applicability of the Cx26 structure to the NT of other connexins are considered. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.
Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA. ecbeyer@uchicago.edu
Eric C
EC
Beyer
Gregory M
GM
Lipkind
John W
JW
Kyle
Viviana M
VM
Berthoud
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D000072259:Connexin 26; D017630:Connexins / Q000737:chemistry* / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009154:Mutation; D010539:Permeability; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D000596:Amino Acids; D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26