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-Structure paper
Title | Insights into autophagosome biogenesis from structural and biochemical analyses of the ATG2A-WIPI4 complex. |
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Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 115, Issue 42, Page E9792-E9801, Year 2018 |
Publish date | Oct 16, 2018 |
Authors | Saikat Chowdhury / Chinatsu Otomo / Alexander Leitner / Kazuto Ohashi / Ruedi Aebersold / Gabriel C Lander / Takanori Otomo / |
PubMed Abstract | Autophagy is an enigmatic cellular process in which double-membrane compartments, called "autophagosomes, form de novo adjacent to the endoplasmic reticulum (ER) and package cytoplasmic contents for ...Autophagy is an enigmatic cellular process in which double-membrane compartments, called "autophagosomes, form de novo adjacent to the endoplasmic reticulum (ER) and package cytoplasmic contents for delivery to lysosomes. Expansion of the precursor membrane phagophore requires autophagy-related 2 (ATG2), which localizes to the PI3P-enriched ER-phagophore junction. We combined single-particle electron microscopy, chemical cross-linking coupled with mass spectrometry, and biochemical analyses to characterize human ATG2A in complex with the PI3P effector WIPI4. ATG2A is a rod-shaped protein that can bridge neighboring vesicles through interactions at each of its tips. WIPI4 binds to one of the tips, enabling the ATG2A-WIPI4 complex to tether a PI3P-containing vesicle to another PI3P-free vesicle. These data suggest that the ATG2A-WIPI4 complex mediates ER-phagophore association and/or tethers vesicles to the ER-phagophore junction, establishing the required organization for phagophore expansion via the transfer of lipid membranes from the ER and/or the vesicles to the phagophore. |
External links | Proc Natl Acad Sci U S A / PubMed:30185561 / PubMed Central |
Methods | EM (single particle) |
Resolution | 29.4 - 30.3 Å |
Structure data | EMDB-8899: EMDB-8900: |
Source |
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