SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Calmodulin association with connexin32-derived peptides suggests trans-domain interaction in chemical gating of gap junction channels

Dodd, R; Peracchia, C; Stolady, D; Török, K (2008) Calmodulin association with connexin32-derived peptides suggests trans-domain interaction in chemical gating of gap junction channels. JOURNAL OF BIOLOGICAL CHEMISTRY, 283 (40). 26911 - 26920. ISSN 0021-9258 https://doi.org/10.1074/jbc.M801434200
SGUL Authors: Torok, Katalin

[img]
Preview
["document_typename_cannot open `/data/SGUL/sgul/eprints3/archives/sgul/documents/disk0/00/00/00/10/18/J.' (No such file or directory) cannot open `Biol.' (No such file or directory) cannot open `Chem.-2008-Dodd-26911-20.pdf' (No such file or directory)" not defined] Published Version
Download (1MB) | Preview

Abstract

Calmodulin plays a key role in the chemical gating of gap junction channels. Two calmodulin-binding regions have previously been identified in connexin32 gap junction protein, one in the N-terminal and another in the C-terminal cytoplasmic tail of the molecule. The aim of this study was to better understand how calmodulin interacts with the connexin32-binding domains. Lobe-specific interactions of calmodulin with connexin32 peptides were studied by stopped flow kinetics, using Ca2+ binding-deficient mutants. Peptides corresponding to the N-terminal tail (residues 1–22) of connexin32 engaged both the N- and C-terminal lobes (N- and C-lobes) of calmodulin, binding with higher affinity to the C-lobe of calmodulin (Ca2+ dissociation rate constants k3,4, 1.7 ± 0.5 s–1) than to the N-lobe (k1,2, 10.8 ± 1.3 s–1). In contrast, peptides representing the C-terminal tail domain (residues 208–227) of connexin32 bound either the C- or the N-lobe but only one calmodulin lobe at a time (k3,4, 2.6 ± 0.1 s–1 or k1, 13.8 ± 0.5 s–1 and k2, 1000 s–1). The calmodulin-binding domains of the N- and C-terminal tails of connexin32 were best defined as residues 1–21 and 216–227, respectively. Our data, showing separate functions of the N- and C-lobes of calmodulin in the interactions with connexin32, suggest trans-domain or trans-subunit bridging by calmodulin as a possible mechanism of gap junction gating.

Item Type: Article
Additional Information: Copyright © 2008, The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice Creative Commons Attribution Non-Commercial License applies to Author Choice Articles
Keywords: Calmodulin, Connexins, Gap Junctions, Humans, Ion Channel Gating, Kinetics, Protein Binding, Protein Structure, Tertiary, Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, BIOCHEMISTRY & MOLECULAR BIOLOGY, CALCIUM, BINDING, ACTIVATION, MECHANISMS, CA2+/CALMODULIN, PERMEABILITY, CONDUCTANCE, DIVERSITY, PROTEINS, KINASE, 06 Biological Sciences, 11 Medical And Health Sciences, 03 Chemical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN: 0021-9258
Related URLs:
Dates:
DateEvent
3 October 2008Published
Web of Science ID: WOS:000259586600011
Download EPMC Full text (HTML)
URI: https://openaccess.sgul.ac.uk/id/eprint/10
Publisher's version: https://doi.org/10.1074/jbc.M801434200

Actions (login required)

Edit Item Edit Item