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The client-binding domain of the cochaperone Sgt2 has a helical-hand structure that binds a short hydrophobic helix

Lin, Ku-Feng and Fry, Michelle Y. and Saladi, Shyam M. and Clemons, William M., Jr. (2019) The client-binding domain of the cochaperone Sgt2 has a helical-hand structure that binds a short hydrophobic helix. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20190114-075410952

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Abstract

The targeting and insertion of tail-anchored (TA) integral membrane proteins (IMP) into the correct membrane is critical for cellular homeostasis. The fungal protein Sgt2, and its human homolog SGTA, binds hydrophobic clients and is the entry point for targeting of ER-bound TA IMPs. Here we reveal molecular details that underlie the mechanism of Sgt2 binding to TA IMP clients. We establish that the Sgt2 C-terminal region is flexible but conserved and sufficient for client binding. A molecular model for this domain reveals a helical hand forming a hydrophobic groove, consistent with a higher affinity for TA IMP clients with hydrophobic faces and a minimal length of 11 residues. This work places Sgt2 into a broader family of TPR-containing co-chaperone proteins.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/517573DOIDiscussion Paper
https://doi.org/10.22002/D1.1100DOIDataset
ORCID:
AuthorORCID
Saladi, Shyam M.0000-0001-9701-3059
Clemons, William M., Jr.0000-0002-0021-889X
Alternate Title:The client-binding domain of the cochaperone SGTA/Sgt2 has a helical-hand structure that binds a short hydrophobic helix
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. bioRxiv preprint first posted online Jan. 10, 2019. Version 2 posted September 16, 2020. We thank D. G. VanderVelde for assistance with NMR data collection; S. Mayo for providing computing resources; S. Shan, H. J. Cho, Y. Liu, and members of the Clemons lab for support and discussion. We thank J. Mock and A. M. Thinn for comments on the manuscript. This work was supported by the National Institutes of Health (NIH) grants GM105385 and GM097572 (to WMC), NIH/National Research Service Award Training Grant GM07616 (to SMS and MYF), and a National Science Foundation Graduate Research fellowship Grant 1144469 (to SMS). Data and Code Availability: All configuration, analysis, and figure generation code employed is available openly at github.com/clemlab/sgt2a-modeling with analysis done in Jupyter Lab/Notebooks using Python 3.6 enabled by Numpy, Pandas, Scikit-Learn, BioPython, and Bokeh [106-111]. The system topology and output files (including trajectory sampled at 0.5 ns intervals) can be permanently found here: 10.22002/D1.1100.
Funders:
Funding AgencyGrant Number
NIHGM105385
NIHGM097572
NIH Predoctoral FellowshipGM07616
NSF Graduate Research FellowshipDGE-1144469
Subject Keywords:Tail-anchored proteins, Protein targeting, co-chaperones, Sti1, Hop
Record Number:CaltechAUTHORS:20190114-075410952
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190114-075410952
Official Citation:The client-binding domain of the cochaperone Sgt2 has a helical-hand structure that binds a short hydrophobic helix. Ku-Feng Lin, Michelle Y. Fry, Shyam M. Saladi, William M. Clemons Jr. bioRxiv 517573; doi: https://doi.org/10.1101/517573
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:92239
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:14 Jan 2019 21:01
Last Modified:21 Sep 2020 22:55

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