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Pathways of allosteric regulation in Hsp70 chaperones
- Source :
- Nature Communications
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Central to the protein folding activity of Hsp70 chaperones is their ability to interact with protein substrates in an ATP-controlled manner, which relies on allosteric regulation between their nucleotide-binding (NBD) and substrate-binding domains (SBD). Here we dissect this mechanism by analysing mutant variants of the Escherichia coli Hsp70 DnaK blocked at distinct steps of allosteric communication. We show that the SBD inhibits ATPase activity by interacting with the NBD through a highly conserved hydrogen bond network, and define the signal transduction pathway that allows bound substrates to trigger ATP hydrolysis. We identify variants deficient in only one direction of allosteric control and demonstrate that ATP-induced substrate release is more important for chaperone activity than substrate-stimulated ATP hydrolysis. These findings provide evidence of an unexpected dichotomic allostery mechanism in Hsp70 chaperones and provide the basis for a comprehensive mechanical model of allostery in Hsp70s.<br />Hsp70 chaperones are essential for cellular proteostasis, and their function depends on allosteric communication between their nucleotide- and substrate-binding domains. Here, Kityk et al. provide a mechanical model of allostery and demonstrate that ATP-induced substrate release is more important for chaperone activity than substrate-stimulated ATP hydrolysis.
- Subjects :
- Allosteric regulation
Mutant
General Physics and Astronomy
Article
General Biochemistry, Genetics and Molecular Biology
chemistry.chemical_compound
Adenosine Triphosphate
Allosteric Regulation
ATP hydrolysis
Escherichia coli
HSP70 Heat-Shock Proteins
Binding site
Adenosine Triphosphatases
Binding Sites
Multidisciplinary
biology
Circular Dichroism
Escherichia coli Proteins
General Chemistry
Allosteric enzyme
chemistry
Biochemistry
Mutagenesis, Site-Directed
biology.protein
Biophysics
Protein folding
Signal transduction
Adenosine triphosphate
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....5e7437ce95995cfcc5bcc53e90ea3d04