ArticleNature communications2023
The GET insertase exhibits conformational plasticity and induces membrane thinning.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- Mammalian MemPrep establishes the lipid composition of ER membranes in HEK293T cells.EMBO reports · 2026Article
- Folding and Oligomerization of CLC Channels and Transporters.Chemical reviews · 2026Review
- Pairwise transmembrane domain insertion during multipass protein biogenesis.Molecular cell · 2026Article
- Molecular basis for the regulation of membrane proteins through preferential lipid solvation.Nature chemical biology · 2026Article
- Membrane Protein Insertion in Cells: Principles, Pathways, and Quality Control.Chemical reviews · 2026Review
- SARS-CoV-2 membrane protein biogenesis.bioRxiv : the preprint server for biology · 2026Article
- SND3 is the membrane insertase within a distinct SEC61 translocon complex.Nature communications · 2025Article
- A phosphoinositide-mediated switch of GET pathway receptor dimerization inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Maintaining the Integral Membrane Proteome: Revisiting the Functional Repertoire of Integral Membrane Proteases.Chembiochem : a European journal of chemical biology · 2025Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The eukaryotic guided entry of tail-anchored proteins (GET) pathway mediates the biogenesis of tail-anchored (TA) membrane proteins at the endoplasmic reticulum. In the cytosol, the Get3 chaperone captures the TA protein substrate and delivers it to the Get1/Get2 membrane protein complex (GET insertase), which then inserts the substrate via a membrane-embedded hydrophilic groove. Here, we present structures, atomistic simulations and functional data of human and Chaetomium thermophilum Get1/Get2/Get3. The core fold of the GET insertase is conserved throughout eukaryotes, whilst thinning of the lipid bilayer occurs in the vicinity of the hydrophilic groove to presumably lower the energetic barrier of membrane insertion. We show that the gating interaction between Get2 helix α3' and Get3 drives conformational changes in both Get3 and the Get1/Get2 membrane heterotetramer. Thus, we provide a framework to understand the conformational plasticity of the GET insertase and how it remodels its membrane environment to promote substrate insertion.
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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.