A Chaperone Lid Ensures Efficient and Privileged Client Transfer during Tail-Anchored Protein Targeting

Un Seng Chio; Sang Yoon Chung; Shimon Weiss; Shu ou Shan

doi:10.1016/j.celrep.2018.12.035

A Chaperone Lid Ensures Efficient and Privileged Client Transfer during Tail-Anchored Protein Targeting

Un Seng Chio, Sang Yoon Chung, Shimon Weiss, Shu ou Shan

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Molecular chaperones play key roles in maintaining cellular proteostasis. In addition to preventing client aggregation, chaperones often relay substrates within a network while preventing off-pathway chaperones from accessing the substrate. Here we show that a conserved lid motif lining the substrate-binding groove of the Get3 ATPase enables these important functions during the targeted delivery of tail-anchored membrane proteins (TAs) to the endoplasmic reticulum. The lid prevents promiscuous TA handoff to off-pathway chaperones, and more importantly, it cooperates with the Get4/5 scaffolding complex to enable rapid and privileged TA transfer from the upstream co-chaperone Sgt2 to Get3. These findings provide a molecular mechanism by which chaperones maintain the pathway specificity of client proteins in the crowded cytosolic environment.

Original language	English
Pages (from-to)	37-44.e7
Journal	Cell Reports
Volume	26
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2018.12.035
State	Published - 2 Jan 2019
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2018 The Authors

Funding

We thank J. Chartron for advice on generating yeast strains using CRISPR-Cas9; R.S. Hegde for CaM expression vectors; H. Cho, M. Rao, F. Liang, A. Siegel, and S. Wang for reagents; S. Hematian and the Beckman Institute Laser Resource Center for training and use of circular dichroism spectrometer; M. Rao for initial observations; and members of the Shan laboratory for critical discussions and comments on the manuscript. This work was supported by Dean Willard Chair funds to S.W., NIH grant GM107368, Gordon and Betty Moore Foundation grant GBMF2939, and a fellowship from the Weston Havens Foundation to S.S. We thank J. Chartron for advice on generating yeast strains using CRISPR-Cas9; R.S. Hegde for CaM expression vectors; H. Cho, M. Rao, F. Liang, A. Siegel, and S. Wang for reagents; S. Hematian and the Beckman Institute Laser Resource Center for training and use of circular dichroism spectrometer; M. Rao for initial observations; and members of the Shan laboratory for critical discussions and comments on the manuscript. This work was supported by Dean Willard Chair funds to S.W., NIH grant GM107368 , Gordon and Betty Moore Foundation grant GBMF2939 , and a fellowship from the Weston Havens Foundation to S.S.

Funders	Funder number
Beckman Institute Laser Resource Center
National Institutes of Health
National Institute of General Medical Sciences	R01GM107368
Gordon and Betty Moore Foundation	GBMF2939
Weston Havens Foundation

Keywords

ATPase
chaperone
membrane protein
protein targeting
tail-anchored protein

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10.1016/j.celrep.2018.12.035

Cite this

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A Chaperone Lid Ensures Efficient and Privileged Client Transfer during Tail-Anchored Protein Targeting

Abstract

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Keywords

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