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A Mechanism of Hsp70 Activation: How J-domains Push Hsp70 into an ATP-Hydrolysis Ready State
Hsp70 chaperones, together with J‑domain protein (JDP) co-chaperones, play a central role in maintaining protein homeostasis within cells. Using structural data and all-atom simulations, we found that when a J-domain binds Hsp70 it gives a “steric push” that changes Hsp70’s conformation. These changes, propagated through coordinated global and local rearrangements, reposition the conserved T199 hydroxyl adjacent to the ATP γ-phosphate, promoting ATP hydrolysis. This explains how J-domain binding powers Hsp70’s chaperone activity. Olewniczak et al. 2026
Image Credit: Michał Olewniczak, Marcin Pitek, Jacek Czub, Jaroslaw Marszalek, Łukasz Nierzwicki, and Bartlomiej Tomiczek
Citation: (2026) PLoS Computational Biology Issue Image | Vol. 22(3) April 2026. PLoS Comput Biol 22(3): ev22.i03. https://doi.org/10.1371/image.pcbi.v22.i03
Published: April 24, 2026
Copyright: © 2026 . This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Hsp70 chaperones, together with J‑domain protein (JDP) co-chaperones, play a central role in maintaining protein homeostasis within cells. Using structural data and all-atom simulations, we found that when a J-domain binds Hsp70 it gives a “steric push” that changes Hsp70’s conformation. These changes, propagated through coordinated global and local rearrangements, reposition the conserved T199 hydroxyl adjacent to the ATP γ-phosphate, promoting ATP hydrolysis. This explains how J-domain binding powers Hsp70’s chaperone activity. Olewniczak et al. 2026
Image Credit: Michał Olewniczak, Marcin Pitek, Jacek Czub, Jaroslaw Marszalek, Łukasz Nierzwicki, and Bartlomiej Tomiczek