The Type I Hsp40 Ydj1 Utilizes a Farnesyl Moiety and Zinc Finger-like Region to Suppress Prion Toxicity

被引:31
作者
Summers, Daniel W. [1 ]
Douglas, Peter M. [1 ]
Ren, Hong-Yu [1 ]
Cyr, Douglas M. [1 ]
机构
[1] Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA
基金
美国国家卫生研究院;
关键词
MOLECULAR CHAPERONE; CO-CHAPERONE; PEPTIDE SUBSTRATE; CRYSTAL-STRUCTURE; HSP70; CHAPERONES; YEAST HSP40; PIN+ PRION; PROTEIN; DNAJ; BINDING;
D O I
10.1074/jbc.M807369200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Type I Hsp40s are molecular chaperones that protect neurons from degeneration by modulating the aggregation state of amyloid-forming proteins. How Type I Hsp40s recognize beta-rich, amyloid-like substrates is currently unknown. Thus, we examined the mechanism for binding between the Type I Hsp40 Ydj1 and the yeast prion [RNQ(+)]. Ydj1 recognized the Gln/Asn-rich prion domain from Rnq1 specifically when it assembled into the amyloid-like [RNQ(+)] prion state. Upon deletion of YDJ1, overexpression of the Rnq1 prion domain killed yeast. Surprisingly, binding and suppression of prion domain toxicity by Ydj1 was dependent upon farnesylation of its C-terminal CAAX box and action of a zinc finger-like region. In contrast, folding of luciferase was independent of farnesylation, yet required the zinc finger-like region of Ydj1 and a conserved hydrophobic peptide-binding pocket. Type I Hsp40s contain at least three different domains that work in concert to bind different protein conformers. The combined action of a farnesyl moiety and zinc finger-like region enable Type I Hsp40s to recognize amyloid-like substrates and prevent formation of cytotoxic protein species.
引用
收藏
页码:3628 / 3639
页数:12
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