Abstract
The mammalian molecular chaperone, HSP60, plays an essential role in protein homeostasis through mediating protein folding and assembly. The structure and ATP-dependent function of HSP60 has been well established in recent studies. After ATP, GTP is the major cellular nucleotide. In this paper, we have investigated the role of GTP in the activity of HSP60. It was found that HSP60 has different properties with respect to allostery, complex formation and protein folding activity depending on the nucleoside triphosphate present. The presence of GTP slightly affected the ATPase activity of HSP60 during protein folding. These results provide clues as to the functional mechanism of the HSP60-HSP10 complex.
Highlights
Molecular chaperones play essential roles in protein homeostasis[1,2]
Based on a comparison with ATP, the HSP60/HSP10 complex mainly formed single-ring structures mostly containing the single-ring complex (HSP607-HSP107) in the presence of GTP. These results suggest that the GTPase activity of HSP60 induces the interaction between HSP60 and HSP10, but hardly induces the the football-type complex compared with the ATPase activity
It has been recently reported that the reaction cycle of the HSP60/HSP10 complex in the presence of ATP is distinct from that of the bacterial chaperonin GroEL/GroES16,18,19
Summary
Molecular chaperones play essential roles in protein homeostasis[1,2]. The protein folding activity of GroEL and its co-chaperone, GroES, have been well characterized both structurally and functionally[3,4,5]. X-ray crystallography demonstrated that HSP60 is converted to a tetradecameric double-ring structure in the presence of ATP, and HSP60 forms a football-type complex when both ATP and the co-chaperone, HSP10, are present[16,17,18] Taken together, these studies strongly indicate that the ATP-dependent functional cycle of the HSP60/HSP10 complex is quite different from that of the bacterial GroEL/ES complex[19]. In comparison to the ATPase activity that produces the stable double-ring structure of HSP60 with HSP10, along with productive refolding of the denatured substrate proteins[16,17,18], the GTPase activity of HSP60 was structurally and functionally quite different. These results demonstrate the importance of the ATPase-dependent cycle of HSP60 in protein folding and a supporting function for the GTPase activity
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
