title: Hsp90 directly interacts, in vitro, with amyloid structures and modulates their assembly and disassembly.
abstract: The 90kDa heat shock protein (Hsp90) participates in regulating the homeostasis of cellular proteins and was considered one of the key chaperones involved in the control and regulation of amyloid deposits. Hsp90 interacts with the amyloid protein tau through tau aggregation-prone regions, including the VQIVYK hexapeptide motif. This hexapeptide, which self-aggregates, forming amyloid fibrils, is widely used to model amyloid formation mechanisms. Despite evidence showing that Hsp90 interacts directly with Ac-VQIVYK-NH2, its role in the hexapeptide fibrillation process and its binding to peptide structures have not yet been determined.
  
  
  
  Various biochemical and biophysical techniques, including ultracentrifugation, spectrophotometry, spectrofluorimetry, and electron microscopy, were employed to assess the effects of Hsp90 on Ac-VQIVYK-NH2 assembly and disassembly processes.
  
  
  
  At sub-stoichiometric concentrations, Hsp90 bound directly to Ac-VQIVYK-NH2 amyloid structures in vitro, with each Hsp90 dimer interacting with an amyloid structure made of around 50 hexapeptide subunits. Hsp90 inhibited Ac-VQIVYK-NH2 assembly by increasing the critical concentrations of Ac-VQIVYK-NH2 required for assembly. Hsp90 also inhibited the disassembly of Ac-VQIVYK-NH2 amyloid fibrils and promoted their rescue.
  
  
  
  A model explaining the dual effect of Hsp90 on the Ac-VQIVYK-NH2 amyloid fibrillation process has been proposed.
  
  
  
  These in vitro results provide new insights into the possible roles of molecular chaperones in modulating amyloid structures by limiting the spread of toxic species.
authors: Translation and Folding, UMR-CNRS 6290, Université de Rennes 1, Campus Beaulieu, 35042 Rennes Cedex, France.
authors: Claire
authors: C
authors: Schirmer
authors: Translation and Folding, UMR-CNRS 6290, Université de Rennes 1, Campus Beaulieu, 35042 Rennes Cedex, France.
authors: Eléonore
authors: E
authors: Lepvrier
authors: Tubulin and Interacting Proteins, UMR-CNRS 6290, Université de Rennes 1, Campus Beaulieu, 35042 Rennes Cedex, France.
authors: Laurence
authors: L
authors: Duchesne
authors: Translation and Folding, UMR-CNRS 6290, Université de Rennes 1, Campus Beaulieu, 35042 Rennes Cedex, France.
authors: Olivier
authors: O
authors: Decaux
authors: Translation and Folding, UMR-CNRS 6290, Université de Rennes 1, Campus Beaulieu, 35042 Rennes Cedex, France.
authors: Daniel
authors: D
authors: Thomas
authors: Translation and Folding, UMR-CNRS 6290, Université de Rennes 1, Campus Beaulieu, 35042 Rennes Cedex, France.
authors: Christian
authors: C
authors: Delamarche
authors: Translation and Folding, UMR-CNRS 6290, Université de Rennes 1, Campus Beaulieu, 35042 Rennes Cedex, France. Electronic address: cyrille.garnier@univ-rennes1.fr.
authors: Cyrille
authors: C
authors: Garnier
mesh_terms: D020816:Amino Acid Motifs; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013552:Swine; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D018841:HSP90 Heat-Shock Proteins; D016875:tau Proteins
keywords: Ac-VQIVYK-NH(2) peptide; Amyloid proteins; Chaperones; Fibrils; Hsp90