PXD048906-1

PXD048906 is an original dataset announced via ProteomeXchange.

Title	Structural basis for lipid transfer by the ATG2A-ATG9A complex
Description	Autophagy 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.
HostingRepository	PRIDE
AnnounceDate	2024-08-17
AnnouncementXML	Submission_2024-08-17_05:32:40.438.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Goran Stjepanovic
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-25 19:34:49	ID requested
⏵ 1	2024-08-17 05:32:40	announced
2	2024-10-22 06:55:20	announced	2024-10-22: Updated project metadata.

10.1038/S41594-024-01376-6;

submitter keyword: LC-MS, XL-MS,Autophagy

Goran Stjepanovic
contact affiliation	Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Shenzhen 518172, China.
contact email	goranstjepanovic@cuhk.edu.cn
lab head
Goran Stjepanovic
contact affiliation	CUHKSZ
contact email	goranstjepanovic@cuhk.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048906
     1. Label: PRIDE project
     2. Name: Structural basis for lipid transfer by the ATG2A-ATG9A complex