Authors: Sulochanadevi Baskaran, Michael J. Ragusa and James H. Hurley

Sulochanadevi Baskaran

Laboratory of Molecular Biology; National Institutes of Diabetes and Digestive and Kidney Diseases; National Institutes of Health; Bethesda, MD USA

Michael J. Ragusa

Laboratory of Molecular Biology; National Institutes of Diabetes and Digestive and Kidney Diseases; National Institutes of Health; Bethesda, MD USA

James H. Hurley

Corresponding author: james.hurley@nih.gov
Laboratory of Molecular Biology; National Institutes of Diabetes and Digestive and Kidney Diseases; National Institutes of Health; Bethesda, MD USA

Abstract:
The key autophagic lipid sensors are Atg18 in yeast and the WIPI proteins in mammals. Atg18 and the WIPIs belong to the PROPPIN family of proteins. PROPPINs are seven- bladed β-propellers that bind to phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2]. In order to understand how PROPPINs bind phosphoinositides, we have determined the crystal structure of a representative, biochemically tractable PROPPIN, Hsv2 of Kluveromyces lactis. The structure revealed that PROPPINs contain two phosphoinositide binding sites which cooperate with a hydrophobic anchoring loop in membrane binding. These three binding elements cooperate in function, as demonstrated by the incremental loss of function in Atg18 mutants impaired in combinations of the two phosphoinositide binding sites and the hydrophobic loop.

Autophagic Punctum to:
S Baskaran, MJ Ragusa, E Boura, JH Hurley. Two-Site Recognition of Phosphatidylinositol 3-Phosphate by PROPPINs in Autophagy. Mol Cell 2012; 47: 339-48
PMID: 22704557 DOI: 10.1016/j.molcel.2012.05.027

Received: July 30, 2012; Accepted: August 27, 2012; Published Online: September 20, 2012

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