8ZQG

Crystal structure of WIPI3 in complex with ATG16L1

Summary for 8ZQG

• Entry DOI: 10.2210/pdb8zqg/pdb
• Descriptor: WD repeat domain phosphoinositide-interacting protein 3, Autophagy-related protein 16-1 (3 entities in total)
• Functional Keywords: wipi3, atg16l1, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 86961.14

Authors

Gong, X.Y.,Pan, L.F. (deposition date: 2024-06-02, release date: 2025-01-01, Last modification date: 2025-01-22)

Primary citation

Gong, X.,Wang, Y.,Zhou, Y.,Pan, L.
Structure of the WIPI3/ATG16L1 Complex Reveals the Molecular Basis for the Recruitment of the ATG12~ATG5-ATG16L1 Complex by WIPI3.
Cells, 13:-, 2024

PubMed 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.

PubMed: 39768203
DOI: 10.3390/cells13242113

Experimental method

X-RAY DIFFRACTION (2.77 Å)