2. Academic Validation
  3. Structural Conservation of the Two Phosphoinositide-Binding Sites in WIPI Proteins

Structural Conservation of the Two Phosphoinositide-Binding Sites in WIPI Proteins

  • J Mol Biol. 2019 Mar 29;431(7):1494-1505. doi: 10.1016/j.jmb.2019.02.019.
Ruobing Liang 1,  Jinqi Ren 2,  Yong Zhang 3,  Wei Feng 4
Affiliations

Affiliations

  • 1 National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China.
  • 3 Key Laboratory of RNA Biology, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China.
  • 4 National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].
PMID: 30797857 DOI: 10.1016/j.jmb.2019.02.019
Abstract

WIPI 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 β-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.

Keywords

PROPPIN; WIPI; autophagy; phosphoinositide; x-ray crystallography.

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