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Bag6 complex contains a minimal tail-anchor–targeting module and a mock BAG domain

Mock, Jee-Young and Chartron, Justin William and Zaslaver, Ma'ayan and Xu, Yue and Ye, Yihong and Clemons, William Melvon, Jr. (2015) Bag6 complex contains a minimal tail-anchor–targeting module and a mock BAG domain. Proceedings of the National Academy of Sciences of the United States of America, 112 (1). pp. 106-111. ISSN 0027-8424. PMCID PMC4291651. http://resolver.caltech.edu/CaltechAUTHORS:20141223-112400838

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Abstract

BCL2-associated athanogene cochaperone 6 (Bag6) plays a central role in cellular homeostasis in a diverse array of processes and is part of the heterotrimeric Bag6 complex, which also includes ubiquitin-like 4A (Ubl4A) and transmembrane domain recognition complex 35 (TRC35). This complex recently has been shown to be important in the TRC pathway, the mislocalized protein degradation pathway, and the endoplasmic reticulum-associated degradation pathway. Here we define the architecture of the Bag6 complex, demonstrating that both TRC35 and Ubl4A have distinct C-terminal binding sites on Bag6 defining a minimal Bag6 complex. A crystal structure of the Bag6–Ubl4A dimer demonstrates that Bag6–BAG is not a canonical BAG domain, and this finding is substantiated biochemically. Remarkably, the minimal Bag6 complex defined here facilitates tail-anchored substrate transfer from small glutamine-rich tetratricopeptide repeat-containing protein α to TRC40. These findings provide structural insight into the complex network of proteins coordinated by Bag6.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.1402745112 DOIArticle
http://www.pnas.org/content/112/1/106.abstractPublisherArticle
http://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1402745112/-/DCSupplementalPublisherSupporting Information
http://www.rcsb.org/pdb/explore/explore.do?structureId=4WWRRelated ItemProtein Data Bank
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291651/PubMed CentralArticle
ORCID:
AuthorORCID
Mock, Jee-Young0000-0002-4656-3357
Clemons, William Melvon, Jr.0000-0002-0021-889X
Additional Information:© 2014 National Academy of Sciences. Edited by Gregory A. Petsko, Weill Cornell Medical College, New York, NY, and approved December 1, 2014 (received for review February 12, 2014). Published online before print December 22, 2014, doi: 10.1073/pnas.1402745112. We thank Daniel Lin and Jens Kaiser for help with data processing; Yoko Shibata and Richard Morimoto (Northwestern University) for plasmids; Michael Rome and Meera Rao for critical reading of the manuscript; members of the W.M.C. laboratory for support and useful discussions; the staff at the Advanced Light Source for assistance with synchrotron data collection; and Gordon and Betty Moore for support of the Molecular Observatory at California Institute of Technology. W.M.C. is supported by National Institutes of Health Grant R01GM097572. Author contributions: J.-Y.M., J.W.C., and W.M.C. designed research; J.-Y.M., J.W.C., M.Z., Y.X., and Y.Y. performed research; M.Z., Y.X., and Y.Y. contributed new reagents/analytic tools; J.-Y.M., Y.Y., and W.M.C. analyzed data; and J.-Y.M. and W.M.C. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. Data deposition: Crystallography, atomic coordinates, and structure factors reported in this paper have been deposited in the Research Collaboratory for Structural Bioinformatics Protein Data Bank, www.rcsb.org/pdb/ (accession no. 4WWR). This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1402745112/-/DCSupplemental.
Funders:
Funding AgencyGrant Number
Gordon and Betty Moore FoundationUNSPECIFIED
NIHR01GM097572
Subject Keywords:GET pathway; Scythe; Bat;3 X-ray crystallography; tail-anchored proteins
PubMed Central ID:PMC4291651
Record Number:CaltechAUTHORS:20141223-112400838
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20141223-112400838
Official Citation:Jee-Young Mock, Justin William Chartron, Ma’ayan Zaslaver, Yue Xu, Yihong Ye, and William Melvon Clemons Jr. Bag6 complex contains a minimal tail-anchor–targeting module and a mock BAG domain PNAS 2015 112 (1) 106-111; published ahead of print December 22, 2014, doi:10.1073/pnas.1402745112
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:53153
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:23 Dec 2014 19:41
Last Modified:18 Oct 2017 23:18

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