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CLIC-2 modulates cardiac ryanodine receptor Ca(2+) release channels

Board, Philip; Coggan, Marjorie; Watson, Sarah; Gage, Peter; Dulhunty, Angela

Description

We have examined the biochemical and functional properties of the recently identified, uncharacterised CLIC-2 protein. Sequence alignments showed that CLIC-2 has a high degree of sequence similarity with CLIC-1 and some similarity to the omega class of glutathione transferases (GSTO). A homology model of CLIC-2 based on the crystal structure of CLIC-1 suggests that CLIC-2 belongs to the GST structural family but, unlike the GSTs, CLIC-2 exists as a monomer. It also has an unusual enzyme...[Show more]

dc.contributor.authorBoard, Philip
dc.contributor.authorCoggan, Marjorie
dc.contributor.authorWatson, Sarah
dc.contributor.authorGage, Peter
dc.contributor.authorDulhunty, Angela
dc.date.accessioned2015-12-13T23:05:19Z
dc.date.available2015-12-13T23:05:19Z
dc.identifier.issn1357-2725
dc.identifier.urihttp://hdl.handle.net/1885/85472
dc.description.abstractWe have examined the biochemical and functional properties of the recently identified, uncharacterised CLIC-2 protein. Sequence alignments showed that CLIC-2 has a high degree of sequence similarity with CLIC-1 and some similarity to the omega class of glutathione transferases (GSTO). A homology model of CLIC-2 based on the crystal structure of CLIC-1 suggests that CLIC-2 belongs to the GST structural family but, unlike the GSTs, CLIC-2 exists as a monomer. It also has an unusual enzyme activity profile. While the CXXC active site motif is conserved between CLIC-2 and the glutaredoxins, no thiol transferase activity was detected. In contrast, low glutathione peroxidase activity was recorded. CLIC-2 was found to be widely distributed in tissues including heart and skeletal muscle. Functional studies showed that CLIC-2 inhibited cardiac ryanodine receptor Ca2+ release channels in lipid bilayers when added to the cytoplasmic side of the channels and inhibited Ca2+ release from cardiac sarcoplasmic reticulum vesicles. The inhibition of RyR channels was reversed by removing CLIC-2 from the solution or by adding an anti-CLIC-2 antibody. The results suggest that one function of CLIC-2 might be to limit Ca2+ release from internal stores in cells.
dc.publisherPergamon-Elsevier Ltd
dc.sourceThe International Journal of Biochemistry and Cell Biology
dc.subjectKeywords: calcium channel; glutaredoxin; protein; protein clic 2; ryanodine receptor; transferase; unclassified drug; animal tissue; article; biochemistry; calcium transport; controlled study; crystal structure; cytoplasm; enzyme activity; heart; lipid bilayer; non CLIC proteins; Cytoplasmic Ca2+ regulation; Glutathione transferase; Ryanodine receptor Ca2+ channels
dc.titleCLIC-2 modulates cardiac ryanodine receptor Ca(2+) release channels
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume36
dc.date.issued2004
local.identifier.absfor060199 - Biochemistry and Cell Biology not elsewhere classified
local.identifier.ariespublicationMigratedxPub13899
local.type.statusPublished Version
local.contributor.affiliationBoard, Philip, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationCoggan, Marjorie, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationWatson, Sarah, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationGage, Peter, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationDulhunty, Angela, College of Medicine, Biology and Environment, ANU
local.bibliographicCitation.startpage1599
local.bibliographicCitation.lastpage1612
local.identifier.doi10.1016/j.biocel.2004.01.026
dc.date.updated2015-12-12T07:59:38Z
local.identifier.scopusID2-s2.0-1942457069
CollectionsANU Research Publications

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