6iyy
From Proteopedia
Crystal structure of human WIPI3,loop deletion mutant
Structural highlights
Disease[WIPI3_HUMAN] The disease may be caused by mutations affecting the gene represented in this entry. Function[WIPI3_HUMAN] Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation (PubMed:28561066). Binds phosphatidylinositol 3-phosphate (PtdIns3P) forming on membranes of the endoplasmic reticulum upon activation of the upstream ULK1 and PI3 kinases and is recruited at phagophore assembly sites where it regulates the elongation of nascent phagophores downstream of WIPI2 (PubMed:28561066). In the cellular response to starvation, may also function together with the TSC1-TSC2 complex and RB1CC1 in the inhibition of the mTORC1 signaling pathway (PubMed:28503735).[1] [2] Publication Abstract from PubMedWIPI proteins are mammalian PROPPIN family members that bind to phosphoinositides and play prominent roles in autophagosome biogenesis. Two phosphoinositide-binding sites were previously described in yeast PROPPIN Hsv2 but remain to be determined in mammalian WIPI proteins. Here, we characterized four human WIPI proteins (WIPI1-4) and solved the structure of WIPI3. WIPI proteins can bind to PI(3)P and PI(3,5)P2 and adopt a conventional seven-bladed beta-propeller fold. The structure of WIPI3 revealed that WIPI proteins also contain two sites embedded in blades 5 and 6 for recognizing phosphoinositides, resembling that in Hsv2. Structural comparison further demonstrated that the two conserved phosphoinositide-binding sites in PROPPIN proteins are not identical but intrinsically tend to recognize different types of phosphoinositides. This work provides the structural evidence to support the conservation of the two phosphoinositide-binding sites in WIPI proteins and also uncovers the potential phosphoinositide-binding selectivity for each site. Structural Conservation of the Two Phosphoinositide-Binding Sites in WIPI Proteins.,Liang R, Ren J, Zhang Y, Feng W J Mol Biol. 2019 Feb 22. pii: S0022-2836(19)30096-8. doi:, 10.1016/j.jmb.2019.02.019. PMID:30797857[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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