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There is evidence that sHsps have a role in suppression of polyQ-induced neurodegeneration; for example, the sHsp alphaB-crystallin (\u03b1B-c) has been identified as a suppressor of SCA3 toxicity in a\n                    <jats:italic>Drosophila<\/jats:italic>\n                    model. However, the molecular mechanism for this suppression is unknown. In this study we tested the ability of \u03b1B-c to suppress the aggregation of a polyQ protein. We found that \u03b1B-c does not inhibit the formation of SDS-insoluble polyQ fibrils. We further tested the effect of \u03b1B-c on the aggregation of ataxin-3, a polyQ protein that aggregates via a two-stage aggregation mechanism. The first stage involves association of the N-terminal Josephin domain followed by polyQ-mediated interactions and the formation of SDS-resistant mature fibrils. Our data show that \u03b1B-c potently inhibits the first stage of ataxin-3 aggregation; however, the second polyQ-dependent stage can still proceed. By using NMR spectroscopy, we have determined that \u03b1B-c interacts with an extensive region on the surface of the Josephin domain. These data provide an example of a domain\/region flanking an amyloidogenic sequence that has a critical role in modulating aggregation of a polypeptide and plays a role in the interaction with molecular chaperones to prevent this aggregation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0914773107","type":"journal-article","created":{"date-parts":[[2010,5,19]],"date-time":"2010-05-19T22:59:53Z","timestamp":1274309993000},"page":"10424-10429","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":77,"title":["Small heat-shock proteins interact with a flanking domain to suppress polyglutamine aggregation"],"prefix":"10.1073","volume":"107","author":[{"given":"Amy L.","family":"Robertson","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3800, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Headey","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M.","family":"Saunders","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3800, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heath","family":"Ecroyd","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Wollongong, Wollongong, New South Wales, 2522, Australia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Scanlon","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Carver","sequence":"additional","affiliation":[{"name":"School of Chemistry and Physics, The University of Adelaide, Adelaide, South Australia, 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Bottomley","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3800, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,5,19]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb993"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-8327-4"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4835(02)00278-6"},{"key":"e_1_3_3_4_2","first-page":"345","article-title":"Accumulation of alpha B-crystallin in central nervous system glia and neurons in pathologic conditions","volume":"140","author":"Iwaki T","year":"1992","unstructured":"T Iwaki, et al., Accumulation of alpha B-crystallin in central nervous system glia and neurons in pathologic conditions. 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