PUBLICATION
Structural insights into metazoan pretargeting GET complexes
- Authors
- Keszei, A.F.A., Yip, M.C.J., Hsieh, T.C., Shao, S.
- ID
- ZDB-PUB-220107-1
- Date
- 2021
- Source
- Nature structural & molecular biology 28: 1029-1037 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Arsenite Transporting ATPases/metabolism*
- Cryoelectron Microscopy
- Endoplasmic Reticulum/metabolism
- Humans
- Models, Molecular
- Molecular Chaperones/metabolism*
- Protein Biosynthesis/physiology*
- Protein Conformation
- Ubiquitins/metabolism
- Zebrafish
- Zebrafish Proteins/metabolism*
- PubMed
- 34887561 Full text @ Nat. Struct. Mol. Biol.
Citation
Keszei, A.F.A., Yip, M.C.J., Hsieh, T.C., Shao, S. (2021) Structural insights into metazoan pretargeting GET complexes. Nature structural & molecular biology. 28:1029-1037.
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 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping