7SQ0

Get3 bound to ADP and the transmembrane domain of the tail-anchored protein Bos1

Summary for 7SQ0

• Entry DOI: 10.2210/pdb7sq0/pdb
• EMDB information: 25373 25374 25375
• Descriptor: ATPase ASNA1 homolog, TMD of the tail-anchored protein Bos1, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: tail-anchored membrane protein targeting deviant walker a atpase targeting factor, chaperone
• Biological source: Giardia intestinalis (strain ATCC 50803 / WB clone C6) (Giardia lamblia); More
• Total number of polymer chains: 3
• Total formula weight: 95158.30

Authors

Fry, M.Y.,Maggiolo, A.O.,Clemons Jr., W.M. (deposition date: 2021-11-04, release date: 2022-07-20, Last modification date: 2025-05-28)

Primary citation

Fry, M.Y.,Najdrova, V.,Maggiolo, A.O.,Saladi, S.M.,Dolezal, P.,Clemons Jr., W.M.
Structurally derived universal mechanism for the catalytic cycle of the tail-anchored targeting factor Get3.
Nat.Struct.Mol.Biol., 29:820-830, 2022

PubMed Abstract: Tail-anchored (TA) membrane proteins, accounting for roughly 2% of proteomes, are primarily targeted posttranslationally to the endoplasmic reticulum membrane by the guided entry of TA proteins (GET) pathway. For this complicated process, it remains unknown how the central targeting factor Get3 uses nucleotide to facilitate large conformational changes to recognize then bind clients while also preventing exposure of hydrophobic surfaces. Here, we identify the GET pathway in Giardia intestinalis and present the structure of the Get3-client complex in the critical postnucleotide-hydrolysis state, demonstrating that Get3 reorganizes the client-binding domain (CBD) to accommodate and shield the client transmembrane helix. Four additional structures of GiGet3, spanning the nucleotide-free (apo) open to closed transition and the ATP-bound state, reveal the details of nucleotide stabilization and occluded CBD. This work resolves key conundrums and allows for a complete model of the dramatic conformational landscape of Get3.

PubMed: 35851188
DOI: 10.1038/s41594-022-00798-4

Experimental method

ELECTRON MICROSCOPY (3.7 Å)