The N-terminal half of the connexin protein contains the core elements of the pore and voltage gates

Jack Kronengold, Miduturu Srinivas, Vytautas Verselis

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Connexins form channels with large aqueous pores that mediate fluxes of inorganic ions and biological signaling molecules. Studies aimed at identifying the connexin pore now include a crystal structure that provides details of putative pore-lining residues that need to be verified using independent biophysical approaches. Here we extended our initial cysteine-scanning studies of the TM1/E1 region of Cx46 hemichannels to include TM2 and TM3 transmembrane segments. No evidence of reactivity was observed in either TM2 or TM3 probed with small or large thiol-modifying reagents. Several identified pore residues in E1 of Cx46 have been verified in different Cx isoforms. Use of variety of thiol reagents indicates that the connexin hemichannel pore is large and flexible enough, at least in the extracellular part of the pore funnel, to accommodate uncommonly large side chains. We also find that that gating characteristics are largely determined by the same domains that constitute the pore. These data indicate that biophysical and structural studies are converging towards a view that the N-terminal half of the Cx protein contains the principal components of the pore and gating elements, with NT, TM1 and E1 forming the pore funnel.

Original languageEnglish (US)
Pages (from-to)453-463
Number of pages11
JournalJournal of Membrane Biology
Volume245
Issue number8
DOIs
StatePublished - Aug 2012

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Connexins
Sulfhydryl Reagents
Proteins
Cysteine
Protein Isoforms
Ions

Keywords

  • Channel pore
  • Chimera
  • Cysteine scanning
  • Hemichannels
  • Voltage gating connexin

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

Cite this

The N-terminal half of the connexin protein contains the core elements of the pore and voltage gates. / Kronengold, Jack; Srinivas, Miduturu; Verselis, Vytautas.

In: Journal of Membrane Biology, Vol. 245, No. 8, 08.2012, p. 453-463.

Research output: Contribution to journalArticle

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