Structural changes in the carboxyl terminus of the gap junction protein connexin40 caused by the interaction with c-Src and zonula occludens-1

Denis Bouvier, Fabien Kieken, Admir Kellezi, Paul L Sorgen

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

c-Src can disrupt the connexin43 (Cx43) and zonula occludens-1 (ZO-1) interaction, leading to down-regulation of gap junction intercellular communication. Previously, the authors characterized the interaction of domains from these proteins with the carboxyl terminus of Cx43 (Cx43CT) and found that binding of the c-Src SH3 domain to Cx43CT disrupted the Cx43CT/ZO-1 PDZ-2 domain complex. Because Cx43 and Cx40 form heteromeric connexons and display similar mechanisms of pH regulation, the authors addressed whether Cx40CT interacts with these domains in a similar manner as Cx43CT. Nuclear magnetic resonance (NMR) data indicate that Cx40CT is an intrinsically disordered protein. NMR titrations determined that PDZ-2 affected the last 28 Cx40CT residues and SH3 shifted numerous amino-terminal Cx40CT residues. Finally, the Cx40CT/PDZ-2 complex was unaffected by SH3 and both domains interacted simultaneously with Cx40CT. This result differs from when the same experiment was performed with Cx43CT, suggesting different mechanisms of regulation exist between connexin isoforms, even when involving the same molecular partners.

Original languageEnglish (US)
Pages (from-to)107-118
Number of pages12
JournalCell Communication and Adhesion
Volume15
Issue number1-2
DOIs
StatePublished - May 1 2008

Fingerprint

Connexin 43
Connexins
Tight Junctions
src Homology Domains
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance
Intrinsically Disordered Proteins
Protein Interaction Domains and Motifs
PDZ Domains
Gap Junctions
Titration
Protein Isoforms
Down-Regulation
Communication
Experiments

Keywords

  • Cx40
  • ZO-1
  • c-Src

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology

Cite this

Structural changes in the carboxyl terminus of the gap junction protein connexin40 caused by the interaction with c-Src and zonula occludens-1. / Bouvier, Denis; Kieken, Fabien; Kellezi, Admir; Sorgen, Paul L.

In: Cell Communication and Adhesion, Vol. 15, No. 1-2, 01.05.2008, p. 107-118.

Research output: Contribution to journalArticle

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