pH-dependent dimerization of the carboxyl terminal domain of Cx43

Paul L Sorgen, Heather S. Duffy, David C. Spray, Mario Delmar

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Previous studies have demonstrated that the carboxyl terminus of the gap junction protein Cx43 (Cx43CT) can act as an independent, regulatory domain that modulates intercellular communication in response to appropriate chemical stimuli. Here, we have used NMR, chemical cross-linking, and analytical ultracentrifugation to further characterize the biochemical and biophysical properties of the Connexin43 carboxyl terminal domain (S255-1382). NMR-diffusion experiments at pH 5.8 suggested that the Connexin43 carboxyl terminus (CX43CT) may have a molecular weight greater than that of a monomer. Sedimentation equilibrium and cross-linking data demonstrated a predominantly dimeric state for the Cx43CT at pH 5.8 and 6.5, with limited dimer formation at a more neutral pH. NMR-filtered nuclear Overhauser effect studies confirmed these observations and identified specific areas of parallel orientation within Cx43CT, likely corresponding to dimerization domains. These regions included a portion of the SH3 binding domain, as well as two fragments previously found to organize in α-helical structures. Together, these data show that acidification causes Cx43CT dimer formation in vitro. Whether dimer formation is an important structural component of the regulation of Connexin43 channels remains to be determined. Dimerization may alter the affinity of Cx43CT regions for specific molecular partners, thus modifying the regulation of gap junction channels.

Original languageEnglish (US)
Pages (from-to)574-581
Number of pages8
JournalBiophysical Journal
Volume87
Issue number1
DOIs
StatePublished - Jan 1 2004

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Connexin 43
Dimerization
Connexins
src Homology Domains
Gap Junctions
Ultracentrifugation
Molecular Weight

ASJC Scopus subject areas

  • Biophysics

Cite this

pH-dependent dimerization of the carboxyl terminal domain of Cx43. / Sorgen, Paul L; Duffy, Heather S.; Spray, David C.; Delmar, Mario.

In: Biophysical Journal, Vol. 87, No. 1, 01.01.2004, p. 574-581.

Research output: Contribution to journalArticle

Sorgen, Paul L ; Duffy, Heather S. ; Spray, David C. ; Delmar, Mario. / pH-dependent dimerization of the carboxyl terminal domain of Cx43. In: Biophysical Journal. 2004 ; Vol. 87, No. 1. pp. 574-581.
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