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J Biol Chem
2009 Dec 04;28449:34257-71. doi: 10.1074/jbc.M109.039594.
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Characterization of the structure and intermolecular interactions between the connexin40 and connexin43 carboxyl-terminal and cytoplasmic loop domains.
Bouvier D
,
Spagnol G
,
Chenavas S
,
Kieken F
,
Vitrac H
,
Brownell S
,
Kellezi A
,
Forge V
,
Sorgen PL
.
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Gap junctions are intercellular channels that allow the passage of ions, small molecules, and second messengers that are essential for the coordination of cellular function. They are formed by two hemichannels, each constituted by the oligomerization of six connexins (Cx). Among the 21 different human Cx isoforms, studies have suggested that in the heart, Cx40 and Cx43 can oligomerize to form heteromeric hemichannels. The mechanism of heteromeric channel regulation has not been clearly defined. Tissue ischemia leads to intracellular acidification and closure of Cx43 and Cx40 homomeric channels. However, coexpression of Cx40 and Cx43 in Xenopus oocytes enhances the pH sensitivity of the channel. This phenomenon requires the carboxyl-terminal (CT) part of both connexins. In this study we used different biophysical methods to determine the structure of the Cx40CT and characterize the Cx40CT/Cx43CT interaction. Our results revealed that the Cx40CT is an intrinsically disordered protein similar to the Cx43CT and that the Cx40CT and Cx43CT can interact. Additionally, we have identified an interaction between the Cx40CT and the cytoplasmic loop of Cx40 as well as between the Cx40CT and the cytoplasmic loop of Cx43 (and vice versa). Our studies support the "particle-receptor" model for pH gating of Cx40 and Cx43 gap junction channels and suggest that interactions between cytoplasmic regulatory domains (both homo- and hetero-connexin) could be important for the regulation of heteromeric channels.
Anumonwo,
The carboxyl terminal domain regulates the unitary conductance and voltage dependence of connexin40 gap junction channels.
2001, Pubmed,
Xenbase
Anumonwo,
The carboxyl terminal domain regulates the unitary conductance and voltage dependence of connexin40 gap junction channels.
2001,
Pubmed
,
Xenbase
Baxter,
Temperature dependence of 1H chemical shifts in proteins.
1997,
Pubmed
Bernstein,
Gap junctions and propagation of the cardiac action potential.
2006,
Pubmed
Bouvier,
Structural changes in the carboxyl terminus of the gap junction protein connexin 40 caused by the interaction with c-Src and zonula occludens-1.
2008,
Pubmed
Bouvier,
(1)H, (13)C, and (15)N backbone resonance assignments of the carboxyl terminal domain of Connexin40.
2007,
Pubmed
Brünger,
Crystallography & NMR system: A new software suite for macromolecular structure determination.
1998,
Pubmed
Bukauskas,
Gating properties of gap junction channels assembled from connexin43 and connexin43 fused with green fluorescent protein.
2001,
Pubmed
Burt,
Alteration of Cx43:Cx40 expression ratio in A7r5 cells.
2001,
Pubmed
Cottrell,
Heterotypic gap junction channel formation between heteromeric and homomeric Cx40 and Cx43 connexons.
2001,
Pubmed
Cottrell,
Cx40 and Cx43 expression ratio influences heteromeric/ heterotypic gap junction channel properties.
2002,
Pubmed
Delaglio,
NMRPipe: a multidimensional spectral processing system based on UNIX pipes.
1995,
Pubmed
Delmar,
Gap junctions as active signaling molecules for synchronous cardiac function.
2000,
Pubmed
Dhein,
Cardiac ischemia and uncoupling: gap junctions in ischemia and infarction.
2006,
Pubmed
Duffy,
pH-dependent intramolecular binding and structure involving Cx43 cytoplasmic domains.
2002,
Pubmed
Duffy,
Regulation of connexin43 protein complexes by intracellular acidification.
2004,
Pubmed
Dunker,
Intrinsic disorder and protein function.
2002,
Pubmed
Dunker,
The protein trinity--linking function and disorder.
2001,
Pubmed
Ek-Vitorín,
PH regulation of connexin43: molecular analysis of the gating particle.
1996,
Pubmed
,
Xenbase
Elenes,
Junctional communication between isolated pairs of canine atrial cells is mediated by homogeneous and heterogeneous gap junction channels.
1999,
Pubmed
Francis,
Connexin diversity and gap junction regulation by pHi.
1999,
Pubmed
,
Xenbase
Gu,
UltraRapid communication : coexpression of connexins 40 and 43 enhances the pH sensitivityof gap junctions: A model for synergistic interactions among connexins.
2000,
Pubmed
,
Xenbase
Gu,
Coexpression of connexins 40 and 43 enhances the pH sensitivity of gap junctions: a model for synergistic interactions among connexins.
2000,
Pubmed
,
Xenbase
He,
Formation of heteromeric gap junction channels by connexins 40 and 43 in vascular smooth muscle cells.
1999,
Pubmed
Hervé,
Pharmacology of cardiovascular gap junctions.
2006,
Pubmed
Hirst-Jensen,
Characterization of the pH-dependent interaction between the gap junction protein connexin43 carboxyl terminus and cytoplasmic loop domains.
2007,
Pubmed
Hoh,
Functional protein domains from the thermally driven motion of polypeptide chains: a proposal.
1998,
Pubmed
Hossain,
Phosphorylated forms of connexin43 predominate in rat brain: demonstration by rapid inactivation of brain metabolism.
1994,
Pubmed
Johnson,
NMR View: A computer program for the visualization and analysis of NMR data.
1994,
Pubmed
Kellezi,
Purification and reconstitution of the connexin43 carboxyl terminus attached to the 4th transmembrane domain in detergent micelles.
2008,
Pubmed
Koval,
Pathways and control of connexin oligomerization.
2006,
Pubmed
Laskowski,
AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR.
1996,
Pubmed
Lees,
CDtool-an integrated software package for circular dichroism spectroscopic data processing, analysis, and archiving.
2004,
Pubmed
Matesic,
Connexin 40 expression in bovine and rat retinas.
2003,
Pubmed
Minezaki,
Intrinsically disordered regions of human plasma membrane proteins preferentially occur in the cytoplasmic segment.
2007,
Pubmed
Morley,
Intramolecular interactions mediate pH regulation of connexin43 channels.
1996,
Pubmed
,
Xenbase
Peters,
Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia.
1997,
Pubmed
Roger,
Disrupted traffic of connexin 43 in human testicular seminoma cells: overexpression of Cx43 induces membrane location and cell proliferation decrease.
2004,
Pubmed
Saffitz,
Closing the gap in understanding the regulation of intercellular communication.
2000,
Pubmed
Seki,
Modifications in the biophysical properties of connexin43 channels by a peptide of the cytoplasmic loop region.
2004,
Pubmed
Sorgen,
pH-dependent dimerization of the carboxyl terminal domain of Cx43.
2004,
Pubmed
Sorgen,
Structural changes in the carboxyl terminus of the gap junction protein connexin43 indicates signaling between binding domains for c-Src and zonula occludens-1.
2004,
Pubmed
Spray,
Physiology and pharmacology of gap junctions.
1985,
Pubmed
Stergiopoulos,
Hetero-domain interactions as a mechanism for the regulation of connexin channels.
1999,
Pubmed
,
Xenbase
Toyofuku,
c-Src regulates the interaction between connexin-43 and ZO-1 in cardiac myocytes.
2001,
Pubmed
Unger,
Three-dimensional structure of a recombinant gap junction membrane channel.
1999,
Pubmed
Valiunas,
Formation of heterotypic gap junction channels by connexins 40 and 43.
2000,
Pubmed
Valiunas,
Gap junction channels formed by coexpressed connexin40 and connexin43.
2001,
Pubmed
VanSlyke,
Analysis of connexin intracellular transport and assembly.
2000,
Pubmed
van Veen,
Physiology of cardiovascular gap junctions.
2006,
Pubmed
Whitmore,
DICHROWEB, an online server for protein secondary structure analyses from circular dichroism spectroscopic data.
2004,
Pubmed
