Rabu, C and Wipf, P and Brodsky, JL and High, S
(2008)
A precursor-specific role for Hsp40/Hsc70 during tail-anchored protein integration at the endoplasmic reticulum.
Journal of Biological Chemistry, 283 (41).
27504 - 27513.
ISSN 0021-9258
Abstract
Tail-anchored (TA) protein synthesis at the endoplasmic reticulum (ER) represents a distinct and novel process that provides a paradigm for understanding post-translational membrane insertion in eukaryotes. The major route for delivering TA proteins to the ER requires both ATP and one or more cytosolic factors that facilitate efficient membrane insertion. Until recently, the identity of these cytosolic components was elusive, but two candidates have now been suggested to promote ATP-dependent TA protein integration. The first is the cytosolic chaperone complex of Hsp40/Hsc70, and the second is a novel ATPase denoted Asna-1 or TRC40. In this study we focus on the role of the Hsp40/Hsc70 complex in promoting TA protein biogenesis at the ER. We show that the membrane integration of most TA proteins is stimulated by Hsp40/Hsc70 when using purified components and a reconstituted system. In contrast, when both Hsp40/Hsc70 and Asna-1/TRC40 are provided as a complete system, small molecule inhibition of Hsp40/Hsc70 indicates that only a subset of TA proteins are obligatory clients for this chaperone-mediated delivery route. We show that the hydrophobicity of the TA region dictates whether a precursor is delivered to the ER via the Hsp40/Hsc70 or Asna-1/TRC40-dependent route, and we conclude that these distinct cytosolic ATPases are responsible for two different ATP-dependent pathways of TA protein biogenesis. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
|
Date: |
10 October 2008 |
Date Type: |
Publication |
Journal or Publication Title: |
Journal of Biological Chemistry |
Volume: |
283 |
Number: |
41 |
Page Range: |
27504 - 27513 |
DOI or Unique Handle: |
10.1074/jbc.m804591200 |
Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
Refereed: |
Yes |
ISSN: |
0021-9258 |
MeSH Headings: |
Adenosine Triphosphate--metabolism; Animals; Arsenite Transporting ATPases--metabolism; Endoplasmic Reticulum--metabolism; HSC70 Heat-Shock Proteins--metabolism; HSP40 Heat-Shock Proteins--metabolism; HeLa Cells; Humans; Hydrophobic and Hydrophilic Interactions; Intracellular Membranes--metabolism; Membrane Proteins--metabolism; Mice; Multiprotein Complexes--metabolism; Protein Structure, Tertiary--physiology; Protein Transport--physiology; Rats |
Other ID: |
NLM PMC2562055 |
PubMed Central ID: |
PMC2562055 |
PubMed ID: |
18667436 |
Date Deposited: |
03 Jul 2013 15:46 |
Last Modified: |
26 Sep 2022 16:27 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/19249 |
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