The type I Hsp40 Ydj1 utilizes a farnesyl moiety and zinc finger-like region to suppress prion toxicity

Daniel W Summers; Peter M Douglas; Hong-Yu Ren; Douglas M Cyr

doi:10.1074/jbc.M807369200

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The type I Hsp40 Ydj1 utilizes a farnesyl moiety and zinc finger-like region to suppress prion toxicity

Journal article

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The type I Hsp40 Ydj1 utilizes a farnesyl moiety and zinc finger-like region to suppress prion toxicity

Daniel W Summers, Peter M Douglas, Hong-Yu Ren and Douglas M Cyr

The Journal of biological chemistry, Vol.284(6), pp.3628-3639

02/06/2009

DOI: 10.1074/jbc.M807369200

PMCID: PMC2635041

PMID: 19056735

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Abstract

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.

Amyloid - genetics

Prions - metabolism

HSP40 Heat-Shock Proteins - metabolism

Prions - genetics

HSP40 Heat-Shock Proteins - genetics

Saccharomyces cerevisiae - genetics

Saccharomyces cerevisiae Proteins - genetics

Saccharomyces cerevisiae - metabolism

Amyloid - metabolism

Saccharomyces cerevisiae Proteins - metabolism

Zinc Fingers - physiology

Protein Prenylation - physiology

Protein Structure, Tertiary - physiology

Details

Title: Subtitle: The type I Hsp40 Ydj1 utilizes a farnesyl moiety and zinc finger-like region to suppress prion toxicity
Creators: Daniel W Summers - Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7090, USA
Peter M Douglas
Hong-Yu Ren
Douglas M Cyr
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.284(6), pp.3628-3639
DOI: 10.1074/jbc.M807369200
PMID: 19056735
PMCID: PMC2635041
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: 5T32GM008581-09 / NIGMS NIH HHS 5R01GM067785-06 / NIGMS NIH HHS R01 GM067785 / NIGMS NIH HHS R01 GM056981 / NIGMS NIH HHS
Language: English
Date published: 02/06/2009
Academic Unit: Iowa Neuroscience Institute; Biology
Record Identifier: 9984070834302771

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