Monitoring the interaction between beta(2)-microglobulin and the molecular chaperone alpha B-crystallin by NMR and mass spectrometry alpha b-crystallin dissociates beta(2)-microglobulin oligomers

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dc.contributor.authorEsposito, Gen_AU
dc.contributor.authorGarvey, Men_AU
dc.contributor.authorAlverdi, Ven_AU
dc.contributor.authorPettirossi, Fen_AU
dc.contributor.authorCorazza, Aen_AU
dc.contributor.authorFogolari, Fen_AU
dc.contributor.authorPolano, Men_AU
dc.contributor.authorMangione, PPen_AU
dc.contributor.authorGiorgetti, Sen_AU
dc.contributor.authorStoppini, Men_AU
dc.contributor.authorRekas, Aen_AU
dc.contributor.authorBellotti, Ven_AU
dc.contributor.authorHeck, AJRen_AU
dc.contributor.authorCarver, JAen_AU
dc.date.accessioned2015-09-30T00:19:23Zen_AU
dc.date.available2015-09-30T00:19:23Zen_AU
dc.date.issued2013-06-14en_AU
dc.date.statistics2013-09-23en_AU
dc.description.abstractThe interaction at neutral pH between wild-type and a variant form (R3A) of the amyloid fibril-forming protein β2-microglobulin (β2m) and the molecular chaperone αB-crystallin was investigated by thioflavin T fluorescence, NMR spectroscopy, and mass spectrometry. Fibril formation of R3Aβ2m was potently prevented by αB-crystallin. αB-crystallin also prevented the unfolding and nonfibrillar aggregation of R3Aβ2m. From analysis of the NMR spectra collected at various R3Aβ2m to αB-crystallin molar subunit ratios, it is concluded that the structured β-sheet core and the apical loops of R3Aβ2m interact in a nonspecific manner with the αB-crystallin. Complementary information was derived from NMR diffusion coefficient measurements of wild-type β2m at a 100-fold concentration excess with respect to αB-crystallin. Mass spectrometry acquired in the native state showed that the onset of wild-type β2m oligomerization was effectively reduced by αB-crystallin. Furthermore, and most importantly, αB-crystallin reversibly dissociated β2m oligomers formed spontaneously in aged samples. These results, coupled with our previous studies, highlight the potent effectiveness of αB-crystallin in preventing β2m aggregation at the various stages of its aggregation pathway. Our findings are highly relevant to the emerging view that molecular chaperone action is intimately involved in the prevention of in vivo amyloid fibril formation. © 2013, The American Society for Biochemistry and Molecular Biology, Inc.en_AU
dc.identifier.citationEsposito, G., Garvey, M., Alverdi, V., Pettirossi, F., Corazza, A., Fogolari, F., Polano, M., Mangione, P. P., Giorgetti, S., Stoppini, M., Rekas, A., Bellotti, V., Heck, A. J. R., & Carver, J. A. (2013). Monitoring the interaction between beta(2)-microglobulin and the molecular chaperone alpha B-crystallin by NMR and mass spectrometry alpha b-crystallin dissociates beta(2)-microglobulin oligomers. Journal of Biological Chemistry, 288(24), 17844-17858. doi:10.1074/jbc.M112.448639en_AU
dc.identifier.govdoc6100en_AU
dc.identifier.issn0021-9258en_AU
dc.identifier.issue24en_AU
dc.identifier.journaltitleJournal of Biological Chemistryen_AU
dc.identifier.pagination17844-17858en_AU
dc.identifier.urihttp://dx.doi.org/10.1074/jbc.M112.448639en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/6261en_AU
dc.identifier.volume288en_AU
dc.language.isoenen_AU
dc.publisherAmerican Society of Biochemistry and Molecular Biologyen_AU
dc.subjectMass spectroscopyen_AU
dc.subjectNuclear magnetic resonanceen_AU
dc.subjectProteinsen_AU
dc.subjectpH valueen_AU
dc.subjectFluorescenceen_AU
dc.subjectNMR spectraen_AU
dc.titleMonitoring the interaction between beta(2)-microglobulin and the molecular chaperone alpha B-crystallin by NMR and mass spectrometry alpha b-crystallin dissociates beta(2)-microglobulin oligomersen_AU
dc.typeJournal Articleen_AU
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