Roles of intramolecular and intermolecular interactions in functional regulation of the Hsp70 J-protein co-chaperone sis1
Abstract
Unlike other Hsp70 molecular chaperones, those of the eukaryotic cytosol have four residues, EEVD, at their C-termini. EEVD(Hsp70) binds adaptor proteins of the Hsp90 chaperone system and mitochondrial membrane preprotein receptors, thereby facilitating processing of Hsp70-bound clients through protein folding and translocation pathways. Among J-protein co-chaperones functioning in these pathways Sis1 is unique, as it also binds the EEVD(Hsp70) motif. However, little is known about the role of the Sis1:EEVD(Hsp70) interaction. We found that deletion of EEVD(Hsp70) abolished the ability of Sis1, but not the ubiquitous J-protein Ydj1, to partner with Hsp70 in in vitro protein refolding. Sis1 co-chaperone activity with Hsp70ΔEEVD was restored upon substitution of a glutamic acid of the J-domain. Structural analysis revealed that this key glutamic acid, which is not present in Ydj1, forms a salt bridge with an arginine of the immediately adjacent glycine-rich region. Thus, restoration of Sis1 in vitro activity suggests that intramolecular interaction(s) between the J-domain and glycine-rich region controls co-chaperone activity, which is optimal only when Sis1 interacts with the EEVD(Hsp70) motif. Yet, we found that disruption of the Sis1:EEVD(Hsp70) interaction enhances the ability of Sis1 to substitute for Ydj1 in vivo. Our results are consistent with the idea that interactionmore »
- Authors:
-
- Univ. of Wisconsin, Madison, WI (United States)
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Univ. of Gdansk and Medical Univ. of Gdansk, Gdansk (Poland)
- Argonne National Lab. (ANL), Argonne, IL (United States); Univ. of Chicago, Chicago, IL (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1263634
- Alternate Identifier(s):
- OSTI ID: 1367767
- Grant/Contract Number:
- AC02-06CH11357; GM31107; GM094585; 2013/09/N/NZ2/01979
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Molecular Biology
- Additional Journal Information:
- Journal Volume: 427; Journal Issue: 7; Journal ID: ISSN 0022-2836
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; molecular chaperone; protein folding; Hsp40; J domain; EEVD motif
Citation Formats
Yu, Hyun Young, Ziegelhoffer, Thomas, Osipiuk, Jerzy, Ciesielski, Szymon J., Baranowski, Maciej, Zhou, Min, Joachimiak, Andrzej, and Craig, Elizabeth A. Roles of intramolecular and intermolecular interactions in functional regulation of the Hsp70 J-protein co-chaperone sis1. United States: N. p., 2015.
Web. doi:10.1016/j.jmb.2015.02.007.
Yu, Hyun Young, Ziegelhoffer, Thomas, Osipiuk, Jerzy, Ciesielski, Szymon J., Baranowski, Maciej, Zhou, Min, Joachimiak, Andrzej, & Craig, Elizabeth A. Roles of intramolecular and intermolecular interactions in functional regulation of the Hsp70 J-protein co-chaperone sis1. United States. https://doi.org/10.1016/j.jmb.2015.02.007
Yu, Hyun Young, Ziegelhoffer, Thomas, Osipiuk, Jerzy, Ciesielski, Szymon J., Baranowski, Maciej, Zhou, Min, Joachimiak, Andrzej, and Craig, Elizabeth A. Fri .
"Roles of intramolecular and intermolecular interactions in functional regulation of the Hsp70 J-protein co-chaperone sis1". United States. https://doi.org/10.1016/j.jmb.2015.02.007. https://www.osti.gov/servlets/purl/1263634.
@article{osti_1263634,
title = {Roles of intramolecular and intermolecular interactions in functional regulation of the Hsp70 J-protein co-chaperone sis1},
author = {Yu, Hyun Young and Ziegelhoffer, Thomas and Osipiuk, Jerzy and Ciesielski, Szymon J. and Baranowski, Maciej and Zhou, Min and Joachimiak, Andrzej and Craig, Elizabeth A.},
abstractNote = {Unlike other Hsp70 molecular chaperones, those of the eukaryotic cytosol have four residues, EEVD, at their C-termini. EEVD(Hsp70) binds adaptor proteins of the Hsp90 chaperone system and mitochondrial membrane preprotein receptors, thereby facilitating processing of Hsp70-bound clients through protein folding and translocation pathways. Among J-protein co-chaperones functioning in these pathways Sis1 is unique, as it also binds the EEVD(Hsp70) motif. However, little is known about the role of the Sis1:EEVD(Hsp70) interaction. We found that deletion of EEVD(Hsp70) abolished the ability of Sis1, but not the ubiquitous J-protein Ydj1, to partner with Hsp70 in in vitro protein refolding. Sis1 co-chaperone activity with Hsp70ΔEEVD was restored upon substitution of a glutamic acid of the J-domain. Structural analysis revealed that this key glutamic acid, which is not present in Ydj1, forms a salt bridge with an arginine of the immediately adjacent glycine-rich region. Thus, restoration of Sis1 in vitro activity suggests that intramolecular interaction(s) between the J-domain and glycine-rich region controls co-chaperone activity, which is optimal only when Sis1 interacts with the EEVD(Hsp70) motif. Yet, we found that disruption of the Sis1:EEVD(Hsp70) interaction enhances the ability of Sis1 to substitute for Ydj1 in vivo. Our results are consistent with the idea that interaction of Sis1 with EEVD(Hsp70) minimizes transfer of Sis1-bound clients to Hsp70s that are primed for client transfer to folding and translocation pathways by their preassociation with EEVD-binding adaptor proteins. Finally, these interactions may be one means by which cells triage Ydj1- and Sis1-bound clients to productive and quality control pathways, respectively.},
doi = {10.1016/j.jmb.2015.02.007},
journal = {Journal of Molecular Biology},
number = 7,
volume = 427,
place = {United States},
year = {Fri Feb 13 00:00:00 EST 2015},
month = {Fri Feb 13 00:00:00 EST 2015}
}
Web of Science
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