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Article: A highly conserved tryptophan in the N-terminal variable domain regulates disulfide bond formation and oligomeric assembly of adiponectin

TitleA highly conserved tryptophan in the N-terminal variable domain regulates disulfide bond formation and oligomeric assembly of adiponectin
Authors
KeywordsAdiponectin
Disulfide Bond
Electron Microscopy
Oligomeric Assembly
W42a Mutant
Issue Date2012
PublisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.febsjournal.org/
Citation
FEBS Journal, 2012, v. 279 n. 14, p. 2495-2507 How to Cite?
AbstractAdiponectin is a collagenous adipokine with direct anti-diabetic and anti-atherogenic properties. It can assume an ensemble of oligomeric states, e.g. trimers, hexamers and octadecamers, each being involved in distinct signaling pathways relevant to adiponectin's diverse biological function in metabolism, immunity, inflammation and cellular homeostasis. Assembly of the active variants principally the octadecameric high molecular weight form is achieved via the tightly controlled oxidation of cysteine 39 located in the adiponectin hyper-variable domain (AHD, residues 18-44) between the signal sequence and the collagen-like domain. We show that mutation of a highly conserved tryptophan (W42A) in the AHD profoundly affects assembly by trapping full-length adiponectin in the oxidized trimeric or hexameric states with a concomitant major reduction in the high molecular weight form. Our biophysical measurements on synthesized analogues of the AHD suggests that the aberrant oligomer distribution can be explained based on the fact that the proximity of W42 to C39 causes a reduction in the rate of C39 oxidation, an effect that to our knowledge has not been documented before. At the biological level, the perturbed oligomer distribution of full-length mutant adiponectin leads to a major reduction in the AMP-activated protein kinase activation in endothelial cells and liver tissues. © 2012 FEBS.
Persistent Identifierhttp://hdl.handle.net/10722/171446
ISSN
2014 Impact Factor: 4.001
2014 SCImago Journal Rankings: 1.866
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorRadjainia, Men_US
dc.contributor.authorHuang, Ben_US
dc.contributor.authorBai, Ben_US
dc.contributor.authorSchmitz, Men_US
dc.contributor.authorYang, SHen_US
dc.contributor.authorHarris, PWRen_US
dc.contributor.authorGriffin, MDWen_US
dc.contributor.authorBrimble, MAen_US
dc.contributor.authorWang, Yen_US
dc.contributor.authorMitra, AKen_US
dc.date.accessioned2012-10-30T06:14:17Z-
dc.date.available2012-10-30T06:14:17Z-
dc.date.issued2012en_US
dc.identifier.citationFEBS Journal, 2012, v. 279 n. 14, p. 2495-2507en_US
dc.identifier.issn1742-464Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/171446-
dc.description.abstractAdiponectin is a collagenous adipokine with direct anti-diabetic and anti-atherogenic properties. It can assume an ensemble of oligomeric states, e.g. trimers, hexamers and octadecamers, each being involved in distinct signaling pathways relevant to adiponectin's diverse biological function in metabolism, immunity, inflammation and cellular homeostasis. Assembly of the active variants principally the octadecameric high molecular weight form is achieved via the tightly controlled oxidation of cysteine 39 located in the adiponectin hyper-variable domain (AHD, residues 18-44) between the signal sequence and the collagen-like domain. We show that mutation of a highly conserved tryptophan (W42A) in the AHD profoundly affects assembly by trapping full-length adiponectin in the oxidized trimeric or hexameric states with a concomitant major reduction in the high molecular weight form. Our biophysical measurements on synthesized analogues of the AHD suggests that the aberrant oligomer distribution can be explained based on the fact that the proximity of W42 to C39 causes a reduction in the rate of C39 oxidation, an effect that to our knowledge has not been documented before. At the biological level, the perturbed oligomer distribution of full-length mutant adiponectin leads to a major reduction in the AMP-activated protein kinase activation in endothelial cells and liver tissues. © 2012 FEBS.en_US
dc.languageengen_US
dc.publisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.febsjournal.org/en_US
dc.relation.ispartofFEBS Journalen_US
dc.subjectAdiponectinen_US
dc.subjectDisulfide Bonden_US
dc.subjectElectron Microscopyen_US
dc.subjectOligomeric Assemblyen_US
dc.subjectW42a Mutanten_US
dc.titleA highly conserved tryptophan in the N-terminal variable domain regulates disulfide bond formation and oligomeric assembly of adiponectinen_US
dc.typeArticleen_US
dc.identifier.emailWang, Y:yuwanghk@hku.hken_US
dc.identifier.authorityWang, Y=rp00239en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1742-4658.2012.08630.xen_US
dc.identifier.pmid22583869-
dc.identifier.scopuseid_2-s2.0-84863463347en_US
dc.identifier.hkuros204755-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84863463347&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume279en_US
dc.identifier.issue14en_US
dc.identifier.spage2495en_US
dc.identifier.epage2507en_US
dc.identifier.isiWOS:000305905300003-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridRadjainia, M=24449842000en_US
dc.identifier.scopusauthoridHuang, B=27169619500en_US
dc.identifier.scopusauthoridBai, B=55240334600en_US
dc.identifier.scopusauthoridSchmitz, M=54416302500en_US
dc.identifier.scopusauthoridYang, SH=55240312200en_US
dc.identifier.scopusauthoridHarris, PWR=7403636042en_US
dc.identifier.scopusauthoridGriffin, MDW=8950502500en_US
dc.identifier.scopusauthoridBrimble, MA=7005581932en_US
dc.identifier.scopusauthoridWang, Y=34973733700en_US
dc.identifier.scopusauthoridMitra, AK=7402543410en_US

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