title: Hsp90 oligomerization process: How can p23 drive the chaperone machineries?
abstract: The 90-kDa heat shock protein (Hsp90) is a highly flexible dimer that is able to self-associate in the presence of divalent cations or under heat shock. In a previous work, we focused on the Mg2+-induced oligomerization process of Hsp90, and characterized the oligomers. Combining analytical ultracentrifugation, size-exclusion chromatography coupled to multi-angle laser light scattering and high-mass matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we studied the interaction of p23 with both Hsp90 dimer and oligomers. Even if p23 predominantly binds the Hsp90 dimer, we demonstrated, for the first time, that p23 is also able to interact with Hsp90 oligomers, shifting the Hsp90 dimer-oligomers equilibrium toward dimer. Our results showed that the Hsp90:p23 binding stoichiometry decreases with the Hsp90 oligomerization degree. Therefore, we propose a model in which p23 would act as a "protein wedge" regarding the Hsp90 dimer closure and the Hsp90 oligomerization process.
authors.affiliation: Translation and Folding, UMR-CNRS 6290, Université de Rennes 1, Campus Beaulieu, 35042 Rennes Cedex, France.
authors.forename: Eléonore
authors.initials: E
authors.lastname: Lepvrier
authors.affiliation: UMR1208 Ingénierie des Agropolymères et Technologies Emergentes INRA-Montpellier SupAgro-CIRAD-Université Montpellier, 2 Place Pierre Viala, F-34060 Montpellier, France.
authors.forename: Michaël
authors.initials: M
authors.lastname: Nigen
authors.affiliation: Translation and Folding, UMR-CNRS 6290, Université de Rennes 1, Campus Beaulieu, 35042 Rennes Cedex, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Moullintraffort
authors.affiliation: Translation and Folding, UMR-CNRS 6290, Université de Rennes 1, Campus Beaulieu, 35042 Rennes Cedex, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Chat
authors.affiliation: Aix-Marseille Université, INSERM UMR 911, Centre de Recherche en Oncologie biologique et Onco-pharmacologie, 13385 Marseille Cedex 5, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Allegro
authors.affiliation: Aix-Marseille Université, INSERM UMR 911, Centre de Recherche en Oncologie biologique et Onco-pharmacologie, 13385 Marseille Cedex 5, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Barbier
authors.affiliation: Translation and Folding, UMR-CNRS 6290, Université de Rennes 1, Campus Beaulieu, 35042 Rennes Cedex, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Thomas
authors.affiliation: CovalX AG, 8952 Schlieren, Zürich, Switzerland.
authors.forename: Alexis
authors.initials: A
authors.lastname: Nazabal
authors.affiliation: Translation and Folding, UMR-CNRS 6290, Université de Rennes 1, Campus Beaulieu, 35042 Rennes Cedex, France. Electronic address: cyrille.garnier@univ-rennes1.fr.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Garnier
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D002234:Carbodiimides / Q000737:chemistry; D002850:Chromatography, Gel; D003432:Cross-Linking Reagents / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D000071876:Prostaglandin-E Synthases; D011485:Protein Binding; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014461:Ultracentrifugation
chemical_list: C518491:1-ethyl-3-(3-(diethylamino)propyl)carbodiimide; D002234:Carbodiimides; D003432:Cross-Linking Reagents; D018841:HSP90 Heat-Shock Proteins; D011994:Recombinant Proteins; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases
keywords: High mass spectrometry; Hsp90; Oligomers; Protein complexes; p23