Mechanics and evolution of Hsp70

Protein allostery requires a communication channel for functional regulation between distal sites within a protein. In the molecular chaperone Hsp70, a two-domain enzyme, the ATP/ADP status of an N-terminal nucleotide-binding domain regulates the substrate affinity of a C-terminal substrate-binding domain. Recently available three-dimensional structures of Hsp70 in ATP/ADP states have provided deep insights into molecular pathways of allosteric signals. However, direct mechanical probing of long-range allosteric coupling between the ATP hydrolysis step and domain states is missing.This work was supported by research grants from the Slovak research and development agency (No. APVV-18-0285), the Slovak Grant Agency VEGA No 1/0024/22, BioPickmol, ITMS2014+: 313011AUW6 supported by the Operational Programme Integrated Infrastructure, funded by the ERDF