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PXD048906

PXD048906 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleStructural basis for lipid transfer by the ATG2A-ATG9A complex
DescriptionAutophagy is characterized by the formation of double-membrane vesicles called autophagosomes. ATG2A and ATG9A play an essential role in autophagy by mediating lipid transfer and re-equilibration between membranes for autophagosome formation. Here we report the cryo-EM structures of human ATG2A-WIPI4 complex at 3.2 Å, and ATG2A-WIPI4-ATG9A complex at 7 Å global resolution. The ATG2A structure is characterized by a central hydrophobic cavity formed by a network of β-strands that facilitates lipid transfer, and highly flexible N- and C-terminal domains. Molecular dynamics simulations of the ATG2A N-terminal domain revealed the mechanism of lipid-extraction from the donor membranes while the ATG2A-ATG9A complex structure provides insights into the later stages of the lipid transfer reaction. ATG9A-ATG2A structural analysis revealed a 3:1 stoichiometry, directly aligning the ATG9A lateral pore with ATG2A lipid transfer cavity, hence allowing for a direct transfer of lipids from ATG2A. The ATG9A trimer can interact with both N- and C-terminal tip of rod-shaped ATG2A. Cryo-electron tomography of ATG2A-liposome binding states shows that ATG2A tethers lipid vesicles at different orientations. In summary, this study provides a molecular basis for the growth of the phagophore membrane, and lends structural insights into spatially coupled lipid transport and re-equilibration during autophagosome formation.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:55:20.582.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGoran Stjepanovic
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-01-25 19:34:49ID requested
12024-08-17 05:32:40announced
22024-10-22 06:55:20announced2024-10-22: Updated project metadata.
Publication List
10.1038/S41594-024-01376-6;
Keyword List
submitter keyword: LC-MS, XL-MS,Autophagy
Contact List
Goran Stjepanovic
contact affiliationKobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Shenzhen 518172, China.
contact emailgoranstjepanovic@cuhk.edu.cn
lab head
Goran Stjepanovic
contact affiliationCUHKSZ
contact emailgoranstjepanovic@cuhk.edu.cn
dataset submitter
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Dataset FTP location
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