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- Title
Structure of the WIPI3/ATG16L1 Complex Reveals the Molecular Basis for the Recruitment of the ATG12~ATG5-ATG16L1 Complex by WIPI3.
- Authors
Gong, Xinyu; Wang, Yingli; Zhou, Yuqian; Pan, Lifeng
- Abstract
Macroautophagy deploys a wealth of autophagy-related proteins to synthesize the double-membrane autophagosome, in order to engulf cytosolic components for lysosome-dependent degradation. The recruitment of the ATG12~ATG5-ATG16L1 complex by WIPI family proteins is a crucial step in autophagosome formation. Nevertheless, the molecular mechanism by which WIPI3 facilitates the recruitment of the ATG12~ATG5-ATG16L1 complex remains largely unknown. Here, we uncover that WIPI3 can directly interact with the coiled-coil domain of ATG16L1. By determining the crystal structure of WIPI3 in complex with ATG16L1 coiled-coil, we elucidate the molecular basis underpinning the specific recruitment of the ATG12~ATG5-ATG16L1 complex by WIPI3. Moreover, we demonstrate that WIPI2 and WIPI3 are competitive for interacting with ATG16L1 coiled-coil, and ATG16L1 and ATG2 are mutually exclusive in binding to WIPI3. In all, our findings provide mechanistic insights into the WIPI3/ATG16L1 interaction, and are valuable for further understanding the activation mechanism of the ATG12~ATG5-ATG16L1 complex as well as the working mode of WIPI3 in autophagy.
- Subjects
CRYSTAL structure; AUTOPHAGY; PROTEINS
- Publication
Cells (2073-4409), 2024, Vol 13, Issue 24, p2113
- ISSN
2073-4409
- Publication type
Academic Journal
- DOI
10.3390/cells13242113