7ru9

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Metazoan pre-targeting GET complex (cBUGG-in)Metazoan pre-targeting GET complex (cBUGG-in)

Structural highlights

7ru9 is a 8 chain structure with sequence from Danio rerio and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.3Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

UBL4A_HUMAN Component of the BAT3 complex, a multiprotein complex involved in the post-translational delivery of tail-anchored (TA) membrane proteins to the endoplasmic reticulum membrane. TA membrane proteins, also named type II transmembrane proteins, contain a single C-terminal transmembrane region. The complex acts by facilitating TA proteins capture by ASNA1/TRC40: it is recruited to ribosomes synthesizing membrane proteins, interacts with the transmembrane region of newly released TA proteins, and transfers them to ASNA1/TRC40 for targeting.[1]

Publication Abstract from PubMed

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 A. 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.

Structural insights into metazoan pretargeting GET complexes.,Keszei AFA, Yip MCJ, Hsieh TC, Shao S Nat Struct Mol Biol. 2021 Dec;28(12):1029-1037. doi: 10.1038/s41594-021-00690-7. , Epub 2021 Dec 9. PMID:34887561[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Mariappan M, Li X, Stefanovic S, Sharma A, Mateja A, Keenan RJ, Hegde RS. A ribosome-associating factor chaperones tail-anchored membrane proteins. Nature. 2010 Aug 26;466(7310):1120-4. doi: 10.1038/nature09296. Epub 2010 Aug 1. PMID:20676083 doi:http://dx.doi.org/10.1038/nature09296
  2. Keszei AFA, Yip MCJ, Hsieh TC, Shao S. Structural insights into metazoan pretargeting GET complexes. Nat Struct Mol Biol. 2021 Dec;28(12):1029-1037. PMID:34887561 doi:10.1038/s41594-021-00690-7

7ru9, resolution 3.30Å

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OCA