- EMDB-24704: Metazoan pre-targeting GET complex with SGTA (partly masked) -
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Basic information
Entry
Database: EMDB / ID: EMD-24704
Title
Metazoan pre-targeting GET complex with SGTA (partly masked)
Map data
sharpened partly masked cBUGGS
Sample
Complex: metazoan pre-targeting GET complex cBUGG-in
Function / homology
Function and homology information
BAT3 complex / immune response-activating cell surface receptor signaling pathway / NK T cell activation / GET complex / ubiquitin-like protein transferase activity / maintenance of unfolded protein / tail-anchored membrane protein insertion into ER membrane / protein carrier chaperone / positive regulation of ERAD pathway / protein insertion into ER membrane ...BAT3 complex / immune response-activating cell surface receptor signaling pathway / NK T cell activation / GET complex / ubiquitin-like protein transferase activity / maintenance of unfolded protein / tail-anchored membrane protein insertion into ER membrane / protein carrier chaperone / positive regulation of ERAD pathway / protein insertion into ER membrane / synaptonemal complex assembly / post-translational protein targeting to endoplasmic reticulum membrane / internal peptidyl-lysine acetylation / misfolded protein binding / endoplasmic reticulum stress-induced pre-emptive quality control / natural killer cell activation / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / proteasome binding / ubiquitin-specific protease binding / regulation of embryonic development / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / polyubiquitin modification-dependent protein binding / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / proteasomal protein catabolic process / synapse assembly / negative regulation of proteolysis / ERAD pathway / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / Hsp70 protein binding / molecular function activator activity / kidney development / lung development / brain development / regulation of protein stability / protein modification process / Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement / chromatin organization / protein-folding chaperone binding / ribosome binding / chromosome / ubiquitin-dependent protein catabolic process / spermatogenesis / molecular adaptor activity / proteasome-mediated ubiquitin-dependent protein catabolic process / cell differentiation / protein stabilization / receptor ligand activity / signaling receptor binding / intracellular membrane-bounded organelle / apoptotic process / ubiquitin protein ligase binding / negative regulation of apoptotic process / nucleolus / ATP hydrolysis activity / extracellular exosome / nucleoplasm / ATP binding / metal ion binding / identical protein binding / nucleus / membrane / cytosol / cytoplasm Similarity search - Function
Ubl4, C-terminal TUGS domain / UBL4A-like, ubiquitin-like domain / Tethering Ubl4a to BAGS domain / Golgi to ER traffic protein 4 / Large proline-rich protein BAG6 / : / Golgi to ER traffic protein 4 / BCL2-associated athanogene 6 / Bag6, BAG-similar domain / : ...Ubl4, C-terminal TUGS domain / UBL4A-like, ubiquitin-like domain / Tethering Ubl4a to BAGS domain / Golgi to ER traffic protein 4 / Large proline-rich protein BAG6 / : / Golgi to ER traffic protein 4 / BCL2-associated athanogene 6 / Bag6, BAG-similar domain / : / Arsenical pump ATPase, ArsA/GET3, eukaryotic / Arsenical pump ATPase, ArsA/GET3 / Anion-transporting ATPase-like domain / Anion-transporting ATPase / Ubiquitin domain signature. / Ubiquitin conserved site / Ubiquitin domain / Ubiquitin family / Ubiquitin homologues / Tetratricopeptide-like helical domain superfamily / Ubiquitin domain profile. / Ubiquitin-like domain / Ubiquitin-like domain superfamily / P-loop containing nucleoside triphosphate hydrolase Similarity search - Domain/homology
Ubiquitin-like protein 4A / Large proline-rich protein BAG6 / ATPase GET3 / Golgi to ER traffic protein 4 homolog Similarity search - Component
Biological species
Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 4.1 Å
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
DP2GM137415
United States
American Heart Association
287375208
United States
Citation
Journal: Nat Struct Mol Biol / Year: 2021 Title: Structural insights into metazoan pretargeting GET complexes. Authors: Alexander F A Keszei / Matthew C J Yip / Ta-Chien Hsieh / Sichen Shao / Abstract: Close coordination between chaperones is essential for protein biosynthesis, including the delivery of tail-anchored (TA) proteins containing a single C-terminal transmembrane domain to the ...Close coordination between chaperones is essential for protein biosynthesis, including the delivery of tail-anchored (TA) proteins containing a single C-terminal transmembrane domain to the endoplasmic reticulum (ER) by the conserved GET pathway. For successful targeting, nascent TA proteins must be promptly chaperoned and loaded onto the cytosolic ATPase Get3 through a transfer reaction involving the chaperone SGTA and bridging factors Get4, Ubl4a and Bag6. Here, we report cryo-electron microscopy structures of metazoan pretargeting GET complexes at 3.3-3.6 Å. The structures reveal that Get3 helix 8 and the Get4 C terminus form a composite lid over the Get3 substrate-binding chamber that is opened by SGTA. Another interaction with Get4 prevents formation of Get3 helix 4, which links the substrate chamber and ATPase domain. Both interactions facilitate TA protein transfer from SGTA to Get3. Our findings show how the pretargeting complex primes Get3 for coordinated client loading and ER targeting.
History
Deposition
Aug 16, 2021
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Header (metadata) release
Jan 19, 2022
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Map release
Jan 19, 2022
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Update
Jan 19, 2022
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Current status
Jan 19, 2022
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
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