6KLR

Crystal structure of human WIPI3 in complex with the WIR-peptide from ATG2A

Summary for 6KLR

• Entry DOI: 10.2210/pdb6klr/pdb
• Descriptor: chimera ATG2A and WIPI3 (2 entities in total)
• Functional Keywords: membrane bound protein, lipid binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 76919.66

Authors

Ren, J.Q.,Liang, R.B.,Feng, W. (deposition date: 2019-07-30, release date: 2020-04-29, Last modification date: 2023-11-22)

Primary citation

Ren, J.,Liang, R.,Wang, W.,Zhang, D.,Yu, L.,Feng, W.
Multi-site-mediated entwining of the linear WIR-motif around WIPI beta-propellers for autophagy.
Nat Commun, 11:2702-2702, 2020

PubMed Abstract: WIPI proteins (WIPI1-4) are mammalian PROPPIN family phosphoinositide effectors essential for autophagosome biogenesis. In addition to phosphoinositides, WIPI proteins can recognize a linear WIPI-interacting-region (WIR)-motif, but the underlying mechanism is poorly understood. Here, we determine the structure of WIPI3 in complex with the WIR-peptide from ATG2A. Unexpectedly, the WIR-peptide entwines around the WIPI3 seven-bladed β-propeller and binds to three sites in blades 1-3. The N-terminal part of the WIR-peptide forms a short strand that augments the periphery of blade 2, the middle segment anchors into an inter-blade hydrophobic pocket between blades 2-3, and the C-terminal aromatic tail wedges into another tailored pocket between blades 1-2. Mutations in three peptide-binding sites disrupt the interactions between WIPI3/4 and ATG2A and impair the ATG2A-mediated autophagic process. Thus, WIPI proteins recognize the WIR-motif by multi-sites in multi-blades and this multi-site-mediated peptide-recognition mechanism could be applicable to other PROPPIN proteins.

PubMed: 32483132
DOI: 10.1038/s41467-020-16523-y

Experimental method

X-RAY DIFFRACTION (2.21 Å)