Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/111715
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dc.contributor.authorJovcevski, B.en
dc.contributor.authorAndrew Aquilina, J.en
dc.contributor.authorBenesch, J.en
dc.contributor.authorEcroyd, H.en
dc.date.issued2018en
dc.identifier.citationCell Stress and Chaperones, 2018; 23(5):827-836en
dc.identifier.issn1355-8145en
dc.identifier.issn1466-1268en
dc.identifier.urihttp://hdl.handle.net/2440/111715-
dc.description.abstractαB-Crystallin (HSPB5) is a small heat-shock protein that is composed of dimers that then assemble into a polydisperse ensemble of oligomers. Oligomerisation is mediated by heterologous interactions between the C-terminal tail of one dimer and the core "α-crystallin" domain of another and stabilised by interactions made by the N-terminal region. Comparatively little is known about the latter contribution, but previous studies have suggested that residues in the region 54-60 form contacts that stabilise the assembly. We have generated mutations in this region (P58A, S59A, S59K, R56S/S59R and an inversion of residues 54-60) to examine their impact on oligomerisation and chaperone activity in vitro. By using native mass spectrometry, we found that all the αB-crystallin mutants were assembly competent, populating similar oligomeric distributions to wild-type, ranging from 16-mers to 30-mers. However, circular dichroism spectroscopy, intrinsic tryptophan and bis-ANS fluorescence studies demonstrated that the secondary structure differs to wild type, the 54-60 inversion mutation having the greatest impact. All the mutants exhibited a dramatic decrease in exposed hydrophobicity. We also found that the mutants in general were equally active as the wild-type protein in inhibiting the amorphous aggregation of insulin and seeded amyloid fibrillation of α-synuclein in vitro, except for the 54-60 inversion mutant, which was significantly less effective at inhibiting insulin aggregation. Our data indicate that alterations in the part of the N-terminal region proximal to the core domain do not drastically affect the oligomerisation of αB-crystallin, reinforcing the robustness of αB-crystallin in functioning as a molecular chaperone.en
dc.description.statementofresponsibilityBlagojce Jovcevski, J. Andrew Aquilina, Justin L.P. Benesch, Heath Ecroyden
dc.language.isoenen
dc.publisherSpringeren
dc.rights© Cell Stress Society International 2018en
dc.subjectProteostasis; molecular chaperone; small heat-shock protein; native mass spectrometry; protein aggregation; αB-crystallin; HSPB5; amyloid fibrilsen
dc.titleThe influence of the N-terminal region proximal to the core domain on the assembly and chaperone activity of αB-crystallinen
dc.typeJournal articleen
dc.identifier.rmid0030083538en
dc.identifier.doi10.1007/s12192-018-0889-yen
dc.relation.granthttp://purl.org/au-research/grants/arc/FT110100586en
dc.relation.granthttp://purl.org/au-research/grants/arc/LE0882289en
dc.identifier.pubid399364-
pubs.library.collectionBiochemistry publicationsen
pubs.library.teamDS14en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidJovcevski, B. [0000-0001-7999-1385]en
Appears in Collections:Biochemistry publications

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