Structural organization of intercellular channels II. Amino terminal domain of the connexins: sequence, functional roles, and structure

• Published in: Biochimica et biophysica acta 2012-08, Vol.1818 (8), p.1823-1830
• Main Authors: Beyer, Eric C., Lipkind, Gregory M., Kyle, John W., Berthoud, Viviana M.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino Acids - chemistry; Animals; Binding Sites; Connexin; Connexins - chemistry; Connexins - physiology; Cytoplasm - metabolism; Gap junction; Gap Junctions - metabolism; Humans; Hydrogen Bonding; Intercellular communication; Models, Molecular; Molecular Conformation; Molecular Sequence Data; Mutation; Permeability; Protein Conformation; Protein Interaction Mapping; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Homology, Amino Acid
• ISSN: 0005-2736; 0006-3002; 1879-2642; 0006-3002
• DOI: 10.1016/j.bbamem.2011.10.011

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. ► The amino terminal (NT) domain of the connexins consists of their first 22–23 amino acids. ► Many NT amino acids are conserved in different connexins. ► The first part of the NT is α-helical, and it lines the wall of the pore. ► NT amino acids are determinants of several channel properties. ► Disease-associated mutations have been identified throughout the connexin NT.