Deutsch
 
Benutzerhandbuch Datenschutzhinweis Impressum Kontakt
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT

Freigegeben

Zeitschriftenartikel

The ATPase cycle of the mitochondrial Hsp90 analog trap1

MPG-Autoren
/persons/resource/persons94057

Leskovar,  Adriane
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons95902

Werbeck,  Nicolas D.
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons94928

Reinstein,  Jochen
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

Externe Ressourcen
Volltexte (frei zugänglich)
Es sind keine frei zugänglichen Volltexte verfügbar
Ergänzendes Material (frei zugänglich)
Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar
Zitation

Leskovar, A., Wegele, H., Werbeck, N. D., Buchner, J., & Reinstein, J. (2008). The ATPase cycle of the mitochondrial Hsp90 analog trap1. The Journal of Biological Chemistry, 283(17), 11677-11688. doi:10.1074/jbc.M709516200.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-002C-06C0-A
Zusammenfassung
Hsp90 is an ATP-dependent molecular chaperone whose mechanism is not yet understood in detail. Here, we present the first ATPase cycle for the mitochondrial member of the Hsp90 family called Trap1 (tumor necrosis factor receptor-associated protein 1). Using biochemical, thermodynamic, and rapid kinetic methods we dissected the kinetics of the nucleotide-regulated rearrangements between the open and the closed conformations. Surprisingly, upon ATP binding, Trap1 shifts predominantly to the closed conformation (70%), but, unlike cytosolic Hsp90 from yeast, this process is rather slow at 0.076 s(-1). Because reopening (0.034 s(-1)) is about ten times faster than hydrolysis (k(hyd) = 0.0039 s(-1)), which is the rate-limiting step, Trap1 is not able to commit ATP to hydrolysis. The proposed ATPase cycle was further scrutinized by a global fitting procedure that utilizes all relevant experimental data simultaneously. This analysis corroborates our model of a two-step binding mechanism of ATP followed by irreversible ATP hydrolysis and a one-step product (ADP) release.