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

Journal of Molecular Biology
Ruobing LiangWei Feng

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.

Citations

Apr 18, 2019·Protein Science : a Publication of the Protein Society·Takuo Osawa, Nobuo N Noda
Aug 19, 2020·Cellular and Molecular Life Sciences : CMLS·Yuqing LeiKefeng Lu
Jul 25, 2019·Molecular Genetics & Genomic Medicine·Qiuhong XiongHan Xiao
Oct 22, 2020·Nature Communications·Hirofumi YamaguchiShigeomi Shimizu
Nov 1, 2020·International Journal of Molecular Sciences·Yiu Wing Sunny CheungCalvin K Yip
Apr 13, 2021·Autophagy·Yingying CongMario Mauthe
May 13, 2021·Proceedings of the National Academy of Sciences of the United States of America·Angeles ArocaDiane C Bassham
Aug 6, 2021·Expert Review of Proteomics·Michael Overduin, Troy A Kervin

❮ Previous
Next ❯

Related Concepts

Related Feeds

ATG proteins

The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.