Search
Abstract
J-domain proteins (JDPs), obligatory Hsp70 cochaperones, play critical roles in protein homeostasis. They promote key allosteric transitions that stabilize Hsp70 interaction with substrate polypeptides upon hydrolysis of its bound ATP. Although a recent crystal structure revealed the physical mode of interaction between a J-domain and an Hsp70, the structural and dynamic consequences of J-domain action once bound and how Hsp70s discriminate among its multiple JDP partners remain enigmatic. We combined free energy simulations, biochemical assays and evolutionary analyses to address these issues. Our results indicate that the invariant aspartate of the J-domain perturbs a conserved intramolecular Hsp70 network of contacts that crosses domains. This perturbation leads to destabilization of the domain-domain interface—thereby promoting the allosteric transition that triggers ATP hydrolysis. While this mechanistic step is driven by conserved residues, evolutionarily variable residues are key to initial JDP/Hsp70 recognition—via electrostatic interactions between oppositely charged surfaces. We speculate that these variable residues allow an Hsp70 to discriminate amongst JDP partners, as many of them have coevolved. Together, our data points to a two-step mode of J-domain action, a recognition stage followed by a mechanistic stage.
Citations
-
1 9
CrossRef
-
0
Web of Science
-
1 9
Scopus
Authors (12)
-
Bartlomiej Tomiczek
-
Wojciech Delewski
-
Milena Stolarska
-
Igor Grochowina
-
Brenda Schilke
-
Rafal Dutkiewicz
-
Marta A. Uzarska
-
Szymon Ciesielski
-
Elizabeth Craig
-
Jaroslaw Marszalek
Cite as
Full text
- Publication version
- Accepted or Published Version
- License
-
open in new tab
Keywords
Details
- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
-
PLoS Computational Biology
no. 16,
ISSN: 1553-7358 - Language:
- English
- Publication year:
- 2020
- Bibliographic description:
- Tomiczek B., Delewski W., Nierzwicki Ł., Stolarska M., Grochowina I., Schilke B., Dutkiewicz R., Uzarska M., Ciesielski S., Czub J., Craig E., Marszalek J.: Two-step mechanism of J-domain action in driving Hsp70 function// PLoS Computational Biology -Vol. 16,iss. 6 (2020), s.e1007913-
- DOI:
- Digital Object Identifier (open in new tab) 10.1371/journal.pcbi.1007913
- Verified by:
- Gdańsk University of Technology
seen 89 times
Recommended for you
Analysis of Reconstituted Tripartite Complex Supports Avidity-based Recruitment of Hsp70 by Substrate Bound J-domain Protein
- M. Jelen,
- I. Grochowina,
- A. Grabinska-Rogala
- + 11 authors
Iron–Sulfur Cluster Biogenesis Chaperones: Evidence for Emergence of Mutational Robustness of a Highly Specific Protein–Protein Interaction
- W. Delewski,
- B. Paterkiewicz,
- M. Manicki
- + 8 authors
Structure and evolution of the 4-helix bundle domain of Zuotin, a J-domain protein co-chaperone of Hsp70
- O. Shrestha,
- R. Sharma,
- B. Tomiczek
- + 10 authors