File Download
  • No File Attached
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: A highly conserved tryptophan in the N-terminal variable domain regulates disulfide bond formation and oligomeric assembly of adiponectin
  • Basic View
  • Metadata View
  • XML View
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
2013 Impact Factor: 3.986
2013 SCImago Journal Rankings: 2.131
 
DOIhttp://dx.doi.org/10.1111/j.1742-4658.2012.08630.x
 
ISI Accession Number IDWOS:000305905300003
 
ReferencesReferences in Scopus
 
DC FieldValue
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.isiWOS:000305905300003
 
dc.identifier.issn1742-464X
2013 Impact Factor: 3.986
2013 SCImago Journal Rankings: 2.131
 
dc.identifier.issue14
 
dc.identifier.pmid22583869
 
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
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Radjainia, M</contributor.author>
<contributor.author>Huang, B</contributor.author>
<contributor.author>Bai, B</contributor.author>
<contributor.author>Schmitz, M</contributor.author>
<contributor.author>Yang, SH</contributor.author>
<contributor.author>Harris, PWR</contributor.author>
<contributor.author>Griffin, MDW</contributor.author>
<contributor.author>Brimble, MA</contributor.author>
<contributor.author>Wang, Y</contributor.author>
<contributor.author>Mitra, AK</contributor.author>
<date.accessioned>2012-10-30T06:14:17Z</date.accessioned>
<date.available>2012-10-30T06:14:17Z</date.available>
<date.issued>2012</date.issued>
<identifier.citation>FEBS Journal, 2012, v. 279 n. 14, p. 2495-2507</identifier.citation>
<identifier.issn>1742-464X</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/171446</identifier.uri>
<description.abstract>Adiponectin 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&apos;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. &#169; 2012 FEBS.</description.abstract>
<language>eng</language>
<publisher>Wiley-Blackwell Publishing Ltd.. The Journal&apos;s web site is located at http://www.febsjournal.org/</publisher>
<relation.ispartof>FEBS Journal</relation.ispartof>
<subject>Adiponectin</subject>
<subject>Disulfide Bond</subject>
<subject>Electron Microscopy</subject>
<subject>Oligomeric Assembly</subject>
<subject>W42a Mutant</subject>
<title>A highly conserved tryptophan in the N-terminal variable domain regulates disulfide bond formation and oligomeric assembly of adiponectin</title>
<type>Article</type>
<description.nature>link_to_subscribed_fulltext</description.nature>
<identifier.doi>10.1111/j.1742-4658.2012.08630.x</identifier.doi>
<identifier.pmid>22583869</identifier.pmid>
<identifier.scopus>eid_2-s2.0-84863463347</identifier.scopus>
<identifier.hkuros>204755</identifier.hkuros>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-84863463347&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>279</identifier.volume>
<identifier.issue>14</identifier.issue>
<identifier.spage>2495</identifier.spage>
<identifier.epage>2507</identifier.epage>
<identifier.isi>WOS:000305905300003</identifier.isi>
<publisher.place>United Kingdom</publisher.place>
</item>
Author Affiliations
  1. The University of Hong Kong
  2. University of Auckland
  3. Bio21 Molecular Science and Biotechnology Institute