6klr | pdb_00006klr
Crystal structure of human WIPI3 in complex with the WIR-peptide from ATG2A
Structural highlights
Function[ATG2A_HUMAN] Involved in autophagosome assembly, regulating the size of nascent autophagosomes (PubMed:28561066). Also regulates lipid droplets morphology and distribution within the cell (PubMed:22219374, PubMed:28561066).[1] [2] Publication Abstract from PubMedWIPI 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 beta-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. Multi-site-mediated entwining of the linear WIR-motif around WIPI beta-propellers for autophagy.,Ren J, Liang R, Wang W, Zhang D, Yu L, Feng W Nat Commun. 2020 Jun 1;11(1):2702. doi: 10.1038/s41467-020-16523-y. PMID:32483132[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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