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https://hdl.handle.net/2440/111715
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dc.contributor.author | Jovcevski, B. | - |
dc.contributor.author | Andrew Aquilina, J. | - |
dc.contributor.author | Benesch, J. | - |
dc.contributor.author | Ecroyd, H. | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Cell Stress and Chaperones, 2018; 23(5):827-836 | - |
dc.identifier.issn | 1355-8145 | - |
dc.identifier.issn | 1466-1268 | - |
dc.identifier.uri | http://hdl.handle.net/2440/111715 | - |
dc.description.abstract | αB-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. | - |
dc.description.statementofresponsibility | Blagojce Jovcevski, J. Andrew Aquilina, Justin L.P. Benesch, Heath Ecroyd | - |
dc.language.iso | en | - |
dc.publisher | Springer | - |
dc.rights | © Cell Stress Society International 2018 | - |
dc.source.uri | http://dx.doi.org/10.1007/s12192-018-0889-y | - |
dc.subject | Proteostasis; molecular chaperone; small heat-shock protein; native mass spectrometry; protein aggregation; αB-crystallin; HSPB5; amyloid fibrils | - |
dc.title | The influence of the N-terminal region proximal to the core domain on the assembly and chaperone activity of αB-crystallin | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1007/s12192-018-0889-y | - |
dc.relation.grant | http://purl.org/au-research/grants/arc/FT110100586 | - |
dc.relation.grant | http://purl.org/au-research/grants/arc/LE0882289 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Jovcevski, B. [0000-0001-7999-1385] | - |
Appears in Collections: | Aurora harvest 8 Biochemistry publications |
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