Protein & Peptide Letters

Prof. Ben M. Dunn  
Department of Biochemistry and Molecular Biology
University of Florida
College of Medicine
P.O. Box 100245
Gainesville, FL
USA
Email: bdunn@ufl.edu

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The Molecular Chaperone Hsp70 Family Members Function by a Bidirectional Heterotrophic Allosteric Mechanism

Author(s): Kelly P. da Silva and Julio C. Borges

Affiliation: Institute of Chemistry of Sao Carlos, University of Sao Paulo-USP, P.O. Box 780–Zip Code 13560-970–Sao Carlos, SP, Brazil.

Abstract:

The Hsp70 family is one of the most important and conserved molecular chaperone families. It is well documented that Hsp70 family members assist many cellular processes involving protein quality control, as follows: protein folding, transport through membranes, protein degradation, escape from aggregation, intracellular signaling, among several others. The Hsp70 proteins act as a cellular pivot capable of receiving and distributing substrates among the other molecular chaperone families. Despite the high identity of the Hsp70 proteins, there are several homologue Hsp70 members that do not have the same role in the cell, which allow them to develop and participate in such large number of activities. The Hsp70 proteins are composed of two main domains: one that binds ATP and hydrolyses it to ADP and another which directly interacts with substrates. These domains present bidirectional heterotrophic allosteric regulation allowing a fine regulated cycle of substrate binding and release. The general mechanism of the Hsp70s cycle is under the control of ATP hydrolysis that modulates the low (ATP-bound state) and high (ADP-bound state) affinity states of Hsp70 for substrates. An important feature of the Hsp70s cycle is that they have several co-chaperones that modulate their cycle and that can also interact and select substrates. Here, we review some known details of the bidirectional heterotrophic allosteric mechanism and other important features for Hsp70s regulating cycle and function.

Keywords: Hsp70, allostery, protein folding, molecular chaperones, heat shock proteins, ATP-bound state, ADP-bound state, homologues, UPS, neurodegenerative diseases, Hsp60/10, Hsp100/ClpB family, Hsc70s, EcDnaK, Thermus thermophilus, NBD, SBD, hydrolysis, adenosine nucleotides, amino acid, T13, NMR, Pi bound, HOP, CHIP, hydrophobic, solvent, NBD-SBD, Crystal, ADP, NEFs, HscA, J-domain, Bag Protein, TPR, Hip, allosterismHsp70, allostery, protein folding, molecular chaperones, heat shock proteins, ATP-bound state, ADP-bound state, homologues, UPS, neurodegenerative diseases, Hsp60/10, Hsp100/ClpB family, Hsc70s, EcDnaK, Thermus thermophilus, NBD, SBD, hydrolysis, adenosine nucleotides, amino acid, T13, NMR, Pi bound, HOP, CHIP, hydrophobic, solvent, NBD-SBD, Crystal, ADP, NEFs, HscA, J-domain, Bag Protein, TPR, Hip, allosterism

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Article Details

VOLUME: 18
ISSUE: 2
Page: [132 - 142]
Pages: 11
DOI: 10.2174/092986611794475057
Price: $58