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ATP-driven molecular chaperone machines.

Clare DK, Saibil HR - Biopolymers (2013)

Bottom Line: This review is focused on the mechanisms by which ATP binding and hydrolysis drive chaperone machines assisting protein folding and unfolding.A survey of the key, general chaperone systems Hsp70 and Hsp90, and the unfoldase Hsp100 is followed by a focus on the Hsp60 chaperonin machine which is understood in most detail.These structures suggest a mechanism by which GroEL can forcefully unfold and then encapsulate substrates for subsequent folding in isolation from all other binding surfaces.

View Article: PubMed Central - PubMed

Affiliation: Department of Crystallography, Institute of Structural and Molecular Biology, Birkbeck College, University of London, Malet Street, London WC1E 7HX, UK.

No MeSH data available.


Conformations of Hsp90. The open (a), partially closed (b), and closed (c) conformations of the Hsp90 dimer (PDB ID: 2IOQ, 2O1U, and 2CG9). The N-terminal domains are shown in red, the middle domains in cyan and the C-terminal domains are shown in blue. Bound nucleotides are in gray.
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fig02: Conformations of Hsp90. The open (a), partially closed (b), and closed (c) conformations of the Hsp90 dimer (PDB ID: 2IOQ, 2O1U, and 2CG9). The N-terminal domains are shown in red, the middle domains in cyan and the C-terminal domains are shown in blue. Bound nucleotides are in gray.

Mentions: Hsp90 has three conserved domains, the ATP binding N-terminal domain, the middle domain and the C-terminal dimerization domain which contains the MEEVD sequence that binds tetratricopeptide (TPR) containing co-chaperones39,40 (Figure 2). Hsp90 functions as a dimer with a single intersubunit contact formed between the C-terminal domains in the absence of nucleotide.41 ATP binding to the open structure induces a lid to close over the nucleotide binding site and the subsequent dimerization of the N-terminal domains forming a closed, twisted, compact conformation.42 In this conformation, a flexible loop in the middle domain of each subunit makes contact with its N-terminal and substrate binding domains and initiates ATP hydrolysis. A potential route for the ATP induced conformational change in the middle domain has been suggested by molecular dynamics.43 Once ATP is hydrolyzed the N-terminal domains dissociate to re-form the open conformation.44 However, the nucleotide states are only weakly coupled to conformation, and the Hsp90 dimer exists in a dynamic equilibrium between open, closed and intermediate states.45,46


ATP-driven molecular chaperone machines.

Clare DK, Saibil HR - Biopolymers (2013)

Conformations of Hsp90. The open (a), partially closed (b), and closed (c) conformations of the Hsp90 dimer (PDB ID: 2IOQ, 2O1U, and 2CG9). The N-terminal domains are shown in red, the middle domains in cyan and the C-terminal domains are shown in blue. Bound nucleotides are in gray.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814418&req=5

fig02: Conformations of Hsp90. The open (a), partially closed (b), and closed (c) conformations of the Hsp90 dimer (PDB ID: 2IOQ, 2O1U, and 2CG9). The N-terminal domains are shown in red, the middle domains in cyan and the C-terminal domains are shown in blue. Bound nucleotides are in gray.
Mentions: Hsp90 has three conserved domains, the ATP binding N-terminal domain, the middle domain and the C-terminal dimerization domain which contains the MEEVD sequence that binds tetratricopeptide (TPR) containing co-chaperones39,40 (Figure 2). Hsp90 functions as a dimer with a single intersubunit contact formed between the C-terminal domains in the absence of nucleotide.41 ATP binding to the open structure induces a lid to close over the nucleotide binding site and the subsequent dimerization of the N-terminal domains forming a closed, twisted, compact conformation.42 In this conformation, a flexible loop in the middle domain of each subunit makes contact with its N-terminal and substrate binding domains and initiates ATP hydrolysis. A potential route for the ATP induced conformational change in the middle domain has been suggested by molecular dynamics.43 Once ATP is hydrolyzed the N-terminal domains dissociate to re-form the open conformation.44 However, the nucleotide states are only weakly coupled to conformation, and the Hsp90 dimer exists in a dynamic equilibrium between open, closed and intermediate states.45,46

Bottom Line: This review is focused on the mechanisms by which ATP binding and hydrolysis drive chaperone machines assisting protein folding and unfolding.A survey of the key, general chaperone systems Hsp70 and Hsp90, and the unfoldase Hsp100 is followed by a focus on the Hsp60 chaperonin machine which is understood in most detail.These structures suggest a mechanism by which GroEL can forcefully unfold and then encapsulate substrates for subsequent folding in isolation from all other binding surfaces.

View Article: PubMed Central - PubMed

Affiliation: Department of Crystallography, Institute of Structural and Molecular Biology, Birkbeck College, University of London, Malet Street, London WC1E 7HX, UK.

No MeSH data available.