Role of heat shock proteins in renal function and adaptation to heat stress: Implications for global warming

Figure 3 Molecular structure of heat shock protein 70[113]. Heat shock protein 70 (HSP70) is a molecular chaperone with two main domains: An N-terminal nucleotide-binding domain (NBD) (approximately 44 kDa) and a C-terminal substrate-binding domain (SBD) (approximately 25-30 kDa), connected by a flexible, conserved linker that facilitates allosteric communication. The NBD consists of two lobes creating a deep cleft for adenosine triphosphate (ATP) binding and hydrolysis, exhibiting a structural fold similar to actin. The SBD is characterized by a β-sandwich subdomain that forms a peptide-binding groove and an α-helical lid that covers the bound substrate. The crucial chaperone function of HSP70 relies on ATP-dependent conformational changes: ATP binding to the NBD leads to an open SBD lid and low substrate affinity, while ATP hydrolysis promotes lid closure and high-affinity substrate binding, enabling HSP70 to act as a molecular machine in protein folding. This figure was adapted with Mol^* (MIT-licensed) from the Structure page for PDB ID 1S3X (CC0 1.0) on the RCSB Protein Data Bank (https://www.rcsb.org/structure/1S3X). Citation: Sriram M, Osipiuk J, Freeman B, Morimoto R, Joachimiak A. Human Hsp70 molecular chaperone binds two calcium ions within the ATPase domain. Structure 1997; 5: 403-414 Copyright ©2002 Elsevier Science Ltd. Published by Elsevier Inc (Supplementary material).