PXD048906

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	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:55:20.582.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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/08/PXD048906

PRIDE project URI

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