Chaperone-assisted protein aggregate reactivation: Different solutions for the same problem

Alejandra Aguado; José Angel Fernández-Higuero; Fernando Moro; Arturo Muga

doi:10.1016/j.abb.2015.07.006

Chaperone-assisted protein aggregate reactivation: Different solutions for the same problem

Arch Biochem Biophys. 2015 Aug 15:580:121-34. doi: 10.1016/j.abb.2015.07.006. Epub 2015 Jul 6.

Authors

Alejandra Aguado¹, José Angel Fernández-Higuero¹, Fernando Moro¹, Arturo Muga²

Affiliations

¹ Unidad de Biofísica (CSIC-UPV/EHU) y Departamento de Bioquímica y Biología Molecular, Facultad de Ciencia y Tecnología, Universidad del País Vasco (UPV/EHU), 48080 Bilbao, Spain.
² Unidad de Biofísica (CSIC-UPV/EHU) y Departamento de Bioquímica y Biología Molecular, Facultad de Ciencia y Tecnología, Universidad del País Vasco (UPV/EHU), 48080 Bilbao, Spain. Electronic address: arturo.muga@ehu.es.

PMID: 26159839
DOI: 10.1016/j.abb.2015.07.006

Abstract

The oligomeric AAA+ chaperones Hsp104 in yeast and ClpB in bacteria are responsible for the reactivation of aggregated proteins, an activity essential for cell survival during severe stress. The protein disaggregase activity of these members of the Hsp100 family is linked to the activity of chaperones from the Hsp70 and Hsp40 families. The precise mechanism by which these proteins untangle protein aggregates remains unclear. Strikingly, Hsp100 proteins are not present in metazoans. This does not mean that animal cells do not have a disaggregase activity, but that this activity is performed by the Hsp70 system and a representative of the Hsp110 family instead of a Hsp100 protein. This review describes the actual view of Hsp100-mediated aggregate reactivation, including the ATP-induced conformational changes associated with their disaggregase activity, the dynamics of the oligomeric assembly that is regulated by its ATPase cycle and the DnaK system, and the tight allosteric coupling between the ATPase domains within the hexameric ring complexes. The lack of homologs of these disaggregases in metazoans has suggested that they might be used as potential targets to develop antimicrobials. The current knowledge of the human disaggregase machinery and the role of Hsp110 are also discussed.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Adenosine Triphosphate / chemistry
Adenosine Triphosphate / metabolism
Allosteric Regulation
Animals
Endopeptidase Clp
Escherichia coli / chemistry
Escherichia coli / genetics
Escherichia coli / metabolism
Escherichia coli Proteins / chemistry*
Escherichia coli Proteins / genetics
Escherichia coli Proteins / metabolism
Gene Expression Regulation
HSP110 Heat-Shock Proteins / chemistry*
HSP110 Heat-Shock Proteins / genetics
HSP110 Heat-Shock Proteins / metabolism
HSP70 Heat-Shock Proteins / chemistry
HSP70 Heat-Shock Proteins / genetics
HSP70 Heat-Shock Proteins / metabolism
Heat-Shock Proteins / chemistry*
Heat-Shock Proteins / genetics
Heat-Shock Proteins / metabolism
Humans
Protein Aggregates*
Protein Conformation
Protein Multimerization
Protein Refolding
Saccharomyces cerevisiae / chemistry
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / chemistry*
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism
Sequence Homology, Amino Acid
Species Specificity

Substances

Escherichia coli Proteins
HSP110 Heat-Shock Proteins
HSP70 Heat-Shock Proteins
Heat-Shock Proteins
Protein Aggregates
Saccharomyces cerevisiae Proteins
HsP104 protein, S cerevisiae
Adenosine Triphosphate
Endopeptidase Clp
dnaK protein, E coli
ClpB protein, E coli