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Importance of cycle timing for the function of the molecular chaperone Hsp90.
Zierer, Bettina K; Rübbelke, Martin; Tippel, Franziska; Madl, Tobias; Schopf, Florian H; Rutz, Daniel A; Richter, Klaus; Sattler, Michael; Buchner, Johannes.
Afiliación
  • Zierer BK; Center for Integrated Protein Science Munich, Department of Chemistry, Technische Universität München, Garching, Germany.
  • Rübbelke M; Center for Integrated Protein Science Munich, Department of Chemistry, Technische Universität München, Garching, Germany.
  • Tippel F; Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany.
  • Madl T; Center for Integrated Protein Science Munich, Department of Chemistry, Technische Universität München, Garching, Germany.
  • Schopf FH; Center for Integrated Protein Science Munich, Department of Chemistry, Technische Universität München, Garching, Germany.
  • Rutz DA; Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany.
  • Richter K; Institute of Molecular Biology &Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.
  • Sattler M; Center for Integrated Protein Science Munich, Department of Chemistry, Technische Universität München, Garching, Germany.
  • Buchner J; Center for Integrated Protein Science Munich, Department of Chemistry, Technische Universität München, Garching, Germany.
Nat Struct Mol Biol ; 23(11): 1020-1028, 2016 Nov.
Article en En | MEDLINE | ID: mdl-27723736
Hsp90 couples ATP hydrolysis to large conformational changes essential for activation of client proteins. The structural transitions involve dimerization of the N-terminal domains and formation of 'closed states' involving the N-terminal and middle domains. Here, we used Hsp90 mutants that modulate ATPase activity and biological function as probes to address the importance of conformational cycling for Hsp90 activity. We found no correlation between the speed of ATP turnover and the in vivo activity of Hsp90: some mutants with almost normal ATPase activity were lethal, and some mutants with lower or undetectable ATPase activity were viable. Our analysis showed that it is crucial for Hsp90 to attain and spend time in certain conformational states: a certain dwell time in open states is required for optimal processing of client proteins, whereas a prolonged population of closed states has negative effects. Thus, the timing of conformational transitions is crucial for Hsp90 function and not cycle speed.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Saccharomyces cerevisiae / Adenosina Trifosfato / Adenosina Trifosfatasas / Proteínas HSP90 de Choque Térmico / Proteínas de Saccharomyces cerevisiae Idioma: En Revista: Nat Struct Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2016 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Saccharomyces cerevisiae / Adenosina Trifosfato / Adenosina Trifosfatasas / Proteínas HSP90 de Choque Térmico / Proteínas de Saccharomyces cerevisiae Idioma: En Revista: Nat Struct Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2016 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos