ATG9A and ATG2A form a heteromeric complex essential for autophagosome formation.
Mol Cell
; 82(22): 4324-4339.e8, 2022 11 17.
Article
in En
| MEDLINE
| ID: mdl-36347259
ABSTRACT
ATG9A and ATG2A are essential core members of the autophagy machinery. ATG9A is a lipid scramblase that allows equilibration of lipids across a membrane bilayer, whereas ATG2A facilitates lipid flow between tethered membranes. Although both have been functionally linked during the formation of autophagosomes, the molecular details and consequences of their interaction remain unclear. By combining data from peptide arrays, crosslinking, and hydrogen-deuterium exchange mass spectrometry together with cryoelectron microscopy, we propose a molecular model of the ATG9A-2A complex. Using this integrative structure modeling approach, we identify several interfaces mediating ATG9A-2A interaction that would allow a direct transfer of lipids from ATG2A into the lipid-binding perpendicular branch of ATG9A. Mutational analyses combined with functional activity assays demonstrate their importance for autophagy, thereby shedding light on this protein complex at the heart of autophagy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
/
Autophagosomes
Type of study:
Prognostic_studies
Language:
En
Journal:
Mol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2022
Document type:
Article
Affiliation country: