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

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TitleA highly conserved tryptophan in the N-terminal variable domain regulates disulfide bond formation and oligomeric assembly of adiponectin
AuthorsRadjainia, M2
Huang, B1
Bai, B1
Schmitz, M2
Yang, SH2
Harris, PWR2
Griffin, MDW3
Brimble, MA2
Wang, Y1
Mitra, AK2
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/
CitationFEBS Journal, 2012, v. 279 n. 14, p. 2495-2507 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1742-4658.2012.08630.x
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.
ISSN1742-464X
2011 Impact Factor: 3.79
2011 SCImago Journal Rankings: 0.326
DOIhttp://dx.doi.org/10.1111/j.1742-4658.2012.08630.x
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorRadjainia, M
dc.contributor.authorHuang, B
dc.contributor.authorBai, B
dc.contributor.authorSchmitz, M
dc.contributor.authorYang, SH
dc.contributor.authorHarris, PWR
dc.contributor.authorGriffin, MDW
dc.contributor.authorBrimble, MA
dc.contributor.authorWang, Y
dc.contributor.authorMitra, AK
dc.date.accessioned2012-10-30T06:14:17Z
dc.date.available2012-10-30T06:14:17Z
dc.date.issued2012
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.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationFEBS Journal, 2012, v. 279 n. 14, p. 2495-2507 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1742-4658.2012.08630.x
dc.identifier.doihttp://dx.doi.org/10.1111/j.1742-4658.2012.08630.x
dc.identifier.epage2507
dc.identifier.hkuros204755
dc.identifier.issn1742-464X
2011 Impact Factor: 3.79
2011 SCImago Journal Rankings: 0.326
dc.identifier.issue14
dc.identifier.scopuseid_2-s2.0-84863463347
dc.identifier.spage2495
dc.identifier.urihttp://hdl.handle.net/10722/171446
dc.identifier.volume279
dc.languageeng
dc.publisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.febsjournal.org/
dc.publisher.placeUnited Kingdom
dc.relation.ispartofFEBS Journal
dc.relation.referencesReferences in Scopus
dc.subjectAdiponectin
dc.subjectDisulfide Bond
dc.subjectElectron Microscopy
dc.subjectOligomeric Assembly
dc.subjectW42a Mutant
dc.titleA highly conserved tryptophan in the N-terminal variable domain regulates disulfide bond formation and oligomeric assembly of adiponectin
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. University of Auckland
  3. Bio21 Molecular Science and Biotechnology Institute