Multiple selection filters ensure accurate tail-anchored membrane protein targeting
- California Institute of Technology, United States
- Howard Hughes Medical Institute, University of California, San Francisco, United States
Abstract
Accurate protein localization is crucial to generate and maintain organization in all cells. Achieving accuracy is challenging, as the molecular signals that dictate a protein's cellular destination are often promiscuous. A salient example is the targeting of an essential class of tail-anchored (TA) proteins, whose sole defining feature is a transmembrane domain near their C-terminus. Here we show that the Guided Entry of Tail-anchored protein (GET) pathway selects TA proteins destined to the endoplasmic reticulum (ER) utilizing distinct molecular steps, including differential binding by the co-chaperone Sgt2 and kinetic proofreading after ATP hydrolysis by the targeting factor Get3. Further, the different steps select for distinct physicochemical features of the TA substrate. The use of multiple selection filters may be general to protein biogenesis pathways that must distinguish correct and incorrect substrates based on minor differences.
Article and author information
Author details
Funding
National Institutes of Health (GM107368)
- Meera Rao
- Un Seng Chio
- Hyunju Cho
- Shu-ou Shan
Howard Hughes Medical Institute
- Peter Walter
Gordon and Betty Moore Foundation (GBMF2939)
- Shu-ou Shan
Leukemia and Lymphoma Society
- Voytek Okreglak
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2016, Rao et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Multiple selection filters ensure accurate tail-anchored membrane protein targeting
eLife 5:e21301.
https://doi.org/10.7554/eLife.21301
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