4EXV

Structure of Kluyveromyces lactis Hsv2p

Summary for 4EXV

• Entry DOI: 10.2210/pdb4exv/pdb
• Descriptor: SVP1-like protein 2, SULFATE ION (2 entities in total)
• Functional Keywords: proppin, wd-repeat, phosphoinosides, phosphatidylinositol, phosphate binding, autophagy, atg2, atg9, atg21, transport protein
• Biological source: Kluyveromyces lactis (yeast)
• Cellular location: Vacuole membrane; Peripheral membrane protein (By similarity): Q6CN23
• Total number of polymer chains: 1
• Total formula weight: 39508.13

Authors

Baskaran, S.,Hurley, J.H. (deposition date: 2012-05-01, release date: 2012-07-04, Last modification date: 2024-02-28)

Primary citation

Baskaran, S.,Ragusa, M.J.,Boura, E.,Hurley, J.H.
Two-Site Recognition of Phosphatidylinositol 3-Phosphate by PROPPINs in Autophagy.
Mol.Cell, 47:339-348, 2012

PubMed 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.

PubMed: 22704557
DOI: 10.1016/j.molcel.2012.05.027

Experimental method

X-RAY DIFFRACTION (3 Å)