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The Bag6 Complex: Biological Complexity through Modularity

Citation

Mock, Jee Young (2017) The Bag6 Complex: Biological Complexity through Modularity. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z91C1TXQ. http://resolver.caltech.edu/CaltechTHESIS:06052017-184553539

Abstract

Proper synthesis and targeting of membrane proteins that contain hydrophobic transmembrane domains are mediated by chaperones and targeting factors. Tail-anchored (TA) proteins are a special class of membrane proteins that are characterized by a single carboxy (C) terminal helix that anchors them to biological membranes. Fungal Guided Entry of Tail-anchored protein (GET) pathway components, which include four soluble proteins—Sgt2, Get3, Get4, Get5—and two membrane bound receptors—Get1 and Get2—mediate TA biogenesis. These proteins maintain TA protein solubility in the aqueous cytosol and target TA to the endoplasmic reticulum. While most of the components are conserved in metazoans, one additional protein, Bag6, reorganizes the sorting complex from the heterotetrameric Get4-5 to the heterotrimeric Bag6-TRC35-Ubl4A. To understand the molecular architecture and mechanism of the Bag6 complex, we took a multidisciplinary approach that combines x-ray crystallography, biochemical reconstitution, and cell biology. Our studies demonstrate that the BAG domain of Bag6 is not a canonical BAG domain. Instead, main role of the Bag6 'mock' BAG domain is to dimerize with Ubl4A. Furthermore, the truncated Bag6 complex defined in this study is sufficient to facilitate substrate transfer from SGTA to TRC40. Lastly, our results unequivocally establish TRC35 as a cytoplasmic retention factor for Bag6. These results provide structural, biochemical and cell biological bases for modular Bag6 function and regulation of nucleocytoplasmic distribution of Bag6 by TRC35.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:GET; TRC; Bag6; Protein Targeting; Protein Quality Control; Tail-Anchored Proteins; X-ray Crystallography; Biochemistry
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Biochemistry and Molecular Biophysics
Thesis Availability:Restricted to Caltech community only
Research Advisor(s):
  • Clemons, William M.
Thesis Committee:
  • Bjorkman, Pamela J. (chair)
  • Chan, David C.
  • Shan, Shu-ou
  • Clemons, William M.
Defense Date:19 May 2017
Record Number:CaltechTHESIS:06052017-184553539
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:06052017-184553539
DOI:10.7907/Z91C1TXQ
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.1402745112DOIArticle adapted for chapter 2 and 3
ORCID:
AuthorORCID
Mock, Jee Young0000-0002-4656-3357
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:10291
Collection:CaltechTHESIS
Deposited By: Jee Young Mock
Deposited On:07 Jun 2017 17:31
Last Modified:07 Jun 2017 17:31

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