title: Prion aggregate structure in yeast cells is determined by the Hsp104-Hsp110 disaggregase machinery.
abstract: Prions consist of misfolded proteins that have adopted an infectious amyloid conformation. In vivo, prion biogenesis is intimately associated with the protein quality control machinery. Using electron tomography, we probed the effects of the heat shock protein Hsp70 chaperone system on the structure of a model yeast [PSI+] prion in situ. Individual Hsp70 deletions shift the balance between fibril assembly and disassembly, resulting in a variable shell of nonfibrillar, but still immobile, aggregates at the surface of the [PSI+] prion deposits. Both Hsp104 (an Hsp100 disaggregase) and Sse1 (the major yeast form of Hsp110) were localized to this surface shell of [PSI+] deposits in the deletion mutants. Elevation of Hsp104 expression promoted the appearance of this novel, nonfibrillar form of the prion aggregate. Moreover, Sse1 was found to regulate prion fibril length. Our studies reveal a key role for Sse1 (Hsp110), in cooperation with Hsp104, in regulating the length and assembly state of [PSI+] prion fibrils in vivo.
authors.affiliation: Crystallography, Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: O'Driscoll
authors.affiliation: Crystallography, Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Clare
authors.affiliation: Crystallography, Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK h.saibil@mail.cryst.bbk.ac.uk.
authors.forename: Helen
authors.initials: H
authors.lastname: Saibil
mesh_terms: D050957:HSP110 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D011328:Prions / Q000378:metabolism* / Q000648:ultrastructure; D066329:Protein Aggregates; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D011328:Prions; D066329:Protein Aggregates; C494656:SSE1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae