title: Coordinated Hsp110 and Hsp104 Activities Power Protein Disaggregation in Saccharomyces cerevisiae.
abstract: Protein aggregation is intimately associated with cellular stress and is accelerated during aging, disease, and cellular dysfunction. Yeast cells rely on the ATP-consuming chaperone Hsp104 to disaggregate proteins together with Hsp70. Hsp110s are ancient and abundant chaperones that form complexes with Hsp70. Here we providein vivodata showing that theSaccharomyces cerevisiaeHsp110s Sse1 and Sse2 are essential for Hsp104-dependent protein disaggregation. Following heat shock, complexes of Hsp110 and Hsp70 are recruited to protein aggregates and function together with Hsp104 in the disaggregation process. In the absence of Hsp110, targeting of Hsp70 and Hsp104 to the aggregates is impaired, and the residual Hsp104 that still reaches the aggregates fails to disaggregate. Thus, coordinated activities of both Hsp104 and Hsp110 are required to reactivate aggregated proteins. These findings have important implications for the understanding of how eukaryotic cells manage misfolded and amyloid proteins.
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Jayasankar Mohanakrishnan
authors.initials: JM
authors.lastname: Kaimal
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Ganapathi
authors.initials: G
authors.lastname: Kandasamy
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Fabian
authors.initials: F
authors.lastname: Gasser
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden claes.andreasson@su.se.
authors.forename: Claes
authors.identifier: http://orcid.org/0000-0001-8948-0685
authors.initials: C
authors.lastname: Andréasson
mesh_terms: D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D050957:HSP110 Heat-Shock Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response; D008156:Luciferases / Q000378:metabolism; D008954:Models, Biological; D010641:Phenotype; D066329:Protein Aggregates; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013696:Temperature
chemical_list: D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D066329:Protein Aggregates; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae; D008156:Luciferases
keywords: Hsp104; Hsp110; Ssa1; Sse1; Sse2; chaperone; heat shock; protein disaggregation; protein folding; protein misfolding; protein quality control; stress proteins