ArticleNature2011
The mechanism of membrane-associated steps in tail-anchored protein insertion.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed.
- Membrane Protein Insertion in Cells: Principles, Pathways, and Quality Control.Chemical reviews · 2026Review
- The ER membrane protein complex acts as a chaperone to promote the biogenesis of multi-bundle membrane proteins.bioRxiv : the preprint server for biology · 2026Article
- ATP13A1 engages SEC61 to facilitate substrate-specific translocation.Science advances · 2025Article
- Calcium modulating ligand confers risk for Parkinson's disease and impacts lysosomes.Annals of clinical and translational neurology · 2025Article
- The formation of chaperone-rich GET bodies depends on the tetratricopeptide repeat region of Sgt2 and is reversed by NADH.Journal of cell science · 2025Article
- FgGET3, an ATPase of the GET Pathway, Is Important for the Development and Virulence ofInternational journal of molecular sciences · 2024Article
- Proteome-wide abundance profiling of yeast deletion strains for GET pathway members using sample multiplexing.Proteomics · 2024Article
- Exploring the molecular composition of the multipass translocon in its native membrane environment.Life science alliance · 2024Article
- A unifying model for membrane protein biogenesis.Nature structural & molecular biology · 2024Review
- A distinct dimer configuration of a diatom Get3 forming a tetrameric complex with its tail-anchored membrane cargo.BMC biology · 2024Article
- Review
- Genome-wide screen identifies new set of genes for improved heterologous laccase expression in Saccharomyces cerevisiae.Microbial cell factories · 2024Article
- Dynamic stability of Sgt2 enables selective and privileged client handover in a chaperone triad.Nature communications · 2024Article
- EMC rectifies the topology of multipass membrane proteins.Nature structural & molecular biology · 2024Article
- The ER membrane protein complex restricts mitophagy by controlling BNIP3 turnover.The EMBO journal · 2024Article
- The GET insertase exhibits conformational plasticity and induces membrane thinning.Nature communications · 2023Article
- A selectivity filter in the ER membrane protein complex limits protein misinsertion at the ER.The Journal of cell biology · 2023Article
- The Biogenesis of Multipass Membrane Proteins.Cold Spring Harbor perspectives in biology · 2023Review
- The ER membrane protein complex governs lysosomal turnover of a mitochondrial tail-anchored protein, BNIP3, to restrict mitophagy.bioRxiv : the preprint server for biology · 2023Article
- A TAle of Two Pathways: Tail-Anchored Protein Insertion at the Endoplasmic Reticulum.Cold Spring Harbor perspectives in biology · 2023Review
45 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
Tail-anchored (TA) membrane proteins destined for the endoplasmic reticulum are chaperoned by cytosolic targeting factors that deliver them to a membrane receptor for insertion. Although a basic framework for TA protein recognition is now emerging, the decisive targeting and membrane insertion steps are not understood. Here we reconstitute the TA protein insertion cycle with purified components, present crystal structures of key complexes between these components and perform mutational analyses based on the structures. We show that a committed targeting complex, formed by a TA protein bound to the chaperone ATPase Get3, is initially recruited to the membrane through an interaction with Get2. Once the targeting complex has been recruited, Get1 interacts with Get3 to drive TA protein release in an ATPase-dependent reaction. After releasing its TA protein cargo, the now-vacant Get3 recycles back to the cytosol concomitant with ATP binding. This work provides a detailed structural and mechanistic framework for the minimal TA protein insertion cycle.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.