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PMID: 22704557 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, U.S. Gov't, Non-P.H.S.

Two-site recognition of phosphatidylinositol 3-phosphate by PROPPINs in autophagy.

Molecular cell ·Vol. 47 ·No. 3 ·2012-08-10 ·Pages 339-48

Baskaran S, Ragusa MJ, Boura E, Hurley JH

Abstract

Macroautophagy is essential to cell survival during starvation and proceeds by the growth of a double-membraned phagophore, which engulfs cytosol and other substrates. The synthesis and recognition of the lipid phosphatidylinositol 3-phosphate, PI(3)P, is essential for autophagy. The key autophagic PI(3)P sensors, which are conserved from yeast to humans, belong to the PROPPIN family. Here we report the crystal structure of the yeast PROPPIN Hsv2. The structure consists of a seven-bladed β-propeller and, unexpectedly, contains two pseudo-equivalent PI(3)P binding sites on blades 5 and 6. These two sites both contribute to membrane binding in vitro and are collectively required for full autophagic function in yeast. These sites function in concert with membrane binding by a hydrophobic loop in blade 6, explaining the specificity of the PROPPINs for membrane-bound PI(3)P. These observations thus provide a structural and mechanistic framework for one of the conserved central molecular recognition events in autophagy.

MeSH Terms
Autophagy/physiology Autophagy-Related Proteins Carrier Proteins/chemistry,metabolism Crystallography, X-Ray Humans Membrane Proteins/chemistry,metabolism Phosphatidylinositol Phosphates/metabolism Protein Structure, Tertiary/physiology Saccharomyces cerevisiae/cytology,metabolism Saccharomyces cerevisiae Proteins/chemistry,metabolism
Chemicals
ATG18 protein, S cerevisiae Autophagy-Related Proteins Carrier Proteins HSV2 protein, S cerevisiae Membrane Proteins Phosphatidylinositol Phosphates Saccharomyces cerevisiae Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Baskaran Sulochanadevi
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Ragusa Michael J
Boura Evzen
Hurley James H
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2012.05.027
Published
2012-08-10
Epub
2012-00-14
Pages
339-48
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC3595537
Subset
IM
Grants
NIGMS NIH HHS · F32 GM099319 · United States
Intramural NIH HHS · ZIA DK075067-01 · United States
NIGMS NIH HHS · GM099319 · United States
Databases
PDB
4EXV
External Links
PubMed source DOI: 10.1016/j.molcel.2012.05.027 PMC Full Text View journal details
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