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The N terminus of connexin37 contains an alpha-helix that is required for channel function.
Kyle JW
,
Berthoud VM
,
Kurutz J
,
Minogue PJ
,
Greenspan M
,
Hanck DA
,
Beyer EC
.
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The cytoplasmic N-terminal domain of connexins has been implicated in multiple aspects of gap junction function, including connexin trafficking/assembly and channel gating. A synthetic peptide corresponding to the first 23 amino acids of human connexin37 was prepared, and circular dichroism and nuclear magnetic resonance studies showed that this N-terminal peptide was predominantly alpha-helical between glycine 5 and glutamate 16. The importance of this structure for localization of the protein at appositional membranes and channel function was tested by expression of site-directed mutants of connexin37 in which amino acids leucine 10 and glutamine 15 were replaced with prolines or alanines. Wild type connexin37 and both substitution mutants localized to appositional membranes between transfected HeLa cells. The proline mutant did not allow intercellular transfer of microinjected neurobiotin; the alanine mutant allowed transfer, but less extensively than wild type connexin37. When expressed alone in Xenopus oocytes, wild type connexin37 produced hemichannel currents, but neither of the double substitution mutants produced detectable currents. The proline mutant (but not the alanine mutant) inhibited co-expressed wild type connexin37. Taken together, our data suggest that the alpha-helical structure of the connexin37 N terminus may be dispensable for protein localization, but it is required for channel and hemichannel function.
Arita,
A novel N14Y mutation in Connexin26 in keratitis-ichthyosis-deafness syndrome: analyses of altered gap junctional communication and molecular structure of N terminus of mutated Connexin26.
2006, Pubmed
Arita,
A novel N14Y mutation in Connexin26 in keratitis-ichthyosis-deafness syndrome: analyses of altered gap junctional communication and molecular structure of N terminus of mutated Connexin26.
2006,
Pubmed
Beahm,
Hemichannel and junctional properties of connexin 50.
2002,
Pubmed
,
Xenbase
Brünger,
Crystallography & NMR system: A new software suite for macromolecular structure determination.
1998,
Pubmed
Common,
Cellular mechanisms of mutant connexins in skin disease and hearing loss.
2003,
Pubmed
D'Andrea,
Hearing loss: frequency and functional studies of the most common connexin26 alleles.
2002,
Pubmed
Deschênes,
Altered trafficking of mutant connexin32.
1997,
Pubmed
Dong,
Role of the N-terminus in permeability of chicken connexin45.6 gap junctional channels.
2006,
Pubmed
Ebihara,
Effect of external magnesium and calcium on human connexin46 hemichannels.
2003,
Pubmed
,
Xenbase
Essenfelder,
Connexin30 mutations responsible for hidrotic ectodermal dysplasia cause abnormal hemichannel activity.
2004,
Pubmed
,
Xenbase
Falk,
High resolution, fluorescence deconvolution microscopy and tagging with the autofluorescent tracers CFP, GFP, and YFP to study the structural composition of gap junctions in living cells.
2001,
Pubmed
Garnier,
GOR method for predicting protein secondary structure from amino acid sequence.
1996,
Pubmed
Geourjon,
SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments.
1995,
Pubmed
Gimlich,
Differential regulation of the levels of three gap junction mRNAs in Xenopus embryos.
1990,
Pubmed
,
Xenbase
Grifa,
Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus.
1999,
Pubmed
,
Xenbase
Kumar,
Molecular biology and genetics of gap junction channels.
1992,
Pubmed
Kyle,
An intact connexin N-terminus is required for function but not gap junction formation.
2008,
Pubmed
,
Xenbase
Lagree,
Specific amino-acid residues in the N-terminus and TM3 implicated in channel function and oligomerization compatibility of connexin43.
2003,
Pubmed
Laird,
Comparative analysis and application of fluorescent protein-tagged connexins.
2001,
Pubmed
Larson,
Functional expression and biochemical characterization of an epitope-tagged connexin37.
2000,
Pubmed
Lin,
An amino-terminal lysine residue of rat connexin40 that is required for spermine block.
2006,
Pubmed
Maeda,
Structure of the connexin 26 gap junction channel at 3.5 A resolution.
2009,
Pubmed
Matsuyama,
Phenotypes of X-linked Charcot-Marie-Tooth disease and altered trafficking of mutant connexin 32 (GJB1).
2001,
Pubmed
Minogue,
An aberrant sequence in a connexin46 mutant underlies congenital cataracts.
2005,
Pubmed
,
Xenbase
Musa,
Amino terminal glutamate residues confer spermine sensitivity and affect voltage gating and channel conductance of rat connexin40 gap junctions.
2004,
Pubmed
Musil,
Biochemical analysis of connexin43 intracellular transport, phosphorylation, and assembly into gap junctional plaques.
1991,
Pubmed
Oh,
Stoichiometry of transjunctional voltage-gating polarity reversal by a negative charge substitution in the amino terminus of a connexin32 chimera.
2000,
Pubmed
,
Xenbase
Oh,
Charges dispersed over the permeation pathway determine the charge selectivity and conductance of a Cx32 chimeric hemichannel.
2008,
Pubmed
,
Xenbase
Oshima,
Roles of Met-34, Cys-64, and Arg-75 in the assembly of human connexin 26. Implication for key amino acid residues for channel formation and function.
2003,
Pubmed
Oshima,
Three-dimensional structure of a human connexin26 gap junction channel reveals a plug in the vestibule.
2007,
Pubmed
Puljung,
Polyvalent cations constitute the voltage gating particle in human connexin37 hemichannels.
2004,
Pubmed
,
Xenbase
Purnick,
Structure of the amino terminus of a gap junction protein.
2000,
Pubmed
,
Xenbase
Purnick,
Reversal of the gating polarity of gap junctions by negative charge substitutions in the N-terminus of connexin 32.
2000,
Pubmed
,
Xenbase
Reed,
Molecular cloning and functional expression of human connexin37, an endothelial cell gap junction protein.
1993,
Pubmed
Ressot,
Connexin32 mutations associated with X-linked Charcot-Marie-Tooth disease show two distinct behaviors: loss of function and altered gating properties.
1998,
Pubmed
,
Xenbase
Richard,
Genetic heterogeneity in erythrokeratodermia variabilis: novel mutations in the connexin gene GJB4 (Cx30.3) and genotype-phenotype correlations.
2003,
Pubmed
Rouan,
Divergent effects of two sequence variants of GJB3 (G12D and R32W) on the function of connexin 31 in vitro.
2003,
Pubmed
Shibayama,
Functional characterization of connexin43 mutations found in patients with oculodentodigital dysplasia.
2005,
Pubmed
Sreerama,
Estimation of protein secondary structure from circular dichroism spectra: comparison of CONTIN, SELCON, and CDSSTR methods with an expanded reference set.
2000,
Pubmed
Sultana,
Zebrafish early cardiac connexin, Cx36.7/Ecx, regulates myofibril orientation and heart morphogenesis by establishing Nkx2.5 expression.
2008,
Pubmed
Thomas,
Cataracts are caused by alterations of a critical N-terminal positive charge in connexin50.
2008,
Pubmed
Tong,
Structural determinants for the differences in voltage gating of chicken Cx56 and Cx45.6 gap-junctional hemichannels.
2006,
Pubmed
,
Xenbase
Tong,
Exchange of gating properties between rat cx46 and chicken cx45.6.
2004,
Pubmed
,
Xenbase
Unger,
Three-dimensional structure of a recombinant gap junction membrane channel.
1999,
Pubmed
Veenstra,
Connexin37 forms high conductance gap junction channels with subconductance state activity and selective dye and ionic permeabilities.
1994,
Pubmed
Verselis,
Opposite voltage gating polarities of two closely related connexins.
1994,
Pubmed
,
Xenbase
Wishart,
Chemical shifts as a tool for structure determination.
1994,
Pubmed
Wong,
Connexin37 protects against atherosclerosis by regulating monocyte adhesion.
2006,
Pubmed
