Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published September 30, 2011 | Supplemental Material + Published
Journal Article Open

A Structural Model of the Sgt2 Protein and Its Interactions with Chaperones and the Get4/Get5 Complex


The insertion of tail-anchored transmembrane (TA) proteins into the appropriate membrane is a post-translational event that requires stabilization of the transmembrane domain and targeting to the proper destination. Sgt2 is a heat-shock protein cognate (HSC) co-chaperone that preferentially binds endoplasmic reticulum-destined TA proteins and directs them to the GET pathway via Get4 and Get5. Here, we present the crystal structure from a fungal Sgt2 homolog of the tetratrico-repeat (TPR) domain and part of the linker that connects to the C-terminal domain. The linker extends into the two-carboxylate clamp of the TPR domain from a symmetry-related molecule mimicking the binding to HSCs. Based on this structure, we provide biochemical evidence that the Sgt2 TPR domain has the ability to directly bind multiple HSC family members. The structure allows us to propose features involved in this lower specificity relative to other TPR containing co-chaperones. We further show that a dimer of Sgt2 binds a single Get5 and use small angle x-ray scattering to characterize the domain arrangement of Sgt2 in solution. These results allow us to present a structural model of the Sgt2-Get4/Get5-HSC complex.

Additional Information

© 2011 by The American Society for Biochemistry and Molecular Biology, Inc. Received June 30, 2011. Revision received July 18, 2011. We thank D. C. Rees and S. O. Shan for critical reading of the manuscript. We thank members of the laboratory for support and useful discussions. We thank Graeme Card, Ana Gonzalez, and Michael Soltice for help with data collection at SSRL BL12-2, Tsutomu Matsui and Hiro Tsuruta for help with data collection and processing at the bioSAXS SSRL BL4-2, and Troy Walton for help with MALLS.Weare grateful to Gordon and Betty Moore for support of the Molecular Observatory at Caltech. This work was supported, in whole or in part, by National Institutes of Health Grant R01GM097572 (to W. M. C.).

Attached Files

Published - Chartron2011p16087J_Biol_Chem.pdf

Supplemental Material - jbc.M111.277798-1.pdf

Supplemental Material - jbc.M111.277798-2.pdf

Supplemental Material - jbc.M111.277798-3.pdf

Supplemental Material - jbc.M111.277798-4.pdf


Files (6.8 MB)
Name Size Download all
2.1 MB Preview Download
521.9 kB Preview Download
1.1 MB Preview Download
3.0 MB Preview Download
124.7 kB Preview Download

Additional details

August 19, 2023
August 19, 2023