Structure and function of the molecular chaperone Hsp104 from yeast

Valerie Grimminger-Marquardt, Hilal A. Lashuel

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The molecular chaperone Hsp104 plays a central role in the clearance of aggregates after heat shock and the propagation of yeast prions. Hsp104's disaggregation activity and prion propagation have been linked to its ability to resolubilize or remodel protein aggregates. However, Hsp104 has also the capacity to catalyze protein aggregation of some substrates at speci.c conditions. Hence, it is a molecular chaperone with two opposing activities with respect to protein aggregation. In yeast models of Huntington's disease, Hsp104 is required for the aggregation and toxicity of polyglutamine (polyQ), but the expression of Hsp104 in cellular and animal models of Huntington's and Parkinson's disease protects against polyQ and α-synuclein toxicity. Therefore, elucidating the molecular determinants and mechanisms underlying the ability of Hsp104 to switch between these two activities is of critical importance for understanding its function and could provide insight into novel strategies aimed at preventing or reversing the formation of toxic protein aggregation in systemic and neurodegenerative protein misfolding diseases. Here, we present an overview of the current molecular models and hypotheses that have been proposed to explain the role of Hsp104 in modulating protein aggregation and prion propagation. The experimental approaches and the evidences presented so far in relation to these models are examined. Our primary objective is to offer a critical review that will inspire the use of novel techniques and the design of new experiments to proceed towards a qualitative and quantitative understanding of the molecular mechanisms underlying the multifunctional properties of Hsp104 in vivo.

Original languageEnglish
Pages (from-to)252-276
Number of pages25
JournalBiopolymers
Volume93
Issue number3
DOIs
Publication statusPublished - 1 Feb 2010
Externally publishedYes

Fingerprint

Molecular Chaperones
Yeast
Aptitude
Agglomeration
Yeasts
Prions
Huntington Disease
Proteins
Proteostasis Deficiencies
Synucleins
Molecular Models
Poisons
Toxicity
Parkinson Disease
Shock
Animal Models
Hot Temperature
Design of experiments
Animals
Switches

Keywords

  • AAA-ATPase
  • Amyloid proteins
  • ClpB
  • Disaggregation
  • Fibril formation
  • Hsp100
  • Hsp104
  • Molecular chaperones
  • Neurodegenerative diseases
  • Protein unfolding by chaperones
  • Yeast prions

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Biomaterials
  • Organic Chemistry

Cite this

Structure and function of the molecular chaperone Hsp104 from yeast. / Grimminger-Marquardt, Valerie; Lashuel, Hilal A.

In: Biopolymers, Vol. 93, No. 3, 01.02.2010, p. 252-276.

Research output: Contribution to journalArticle

Grimminger-Marquardt, V & Lashuel, HA 2010, 'Structure and function of the molecular chaperone Hsp104 from yeast', Biopolymers, vol. 93, no. 3, pp. 252-276. https://doi.org/10.1002/bip.21301
Grimminger-Marquardt, Valerie ; Lashuel, Hilal A. / Structure and function of the molecular chaperone Hsp104 from yeast. In: Biopolymers. 2010 ; Vol. 93, No. 3. pp. 252-276.
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