Crystal Structure of the Yeast Phox Homology (PX) Domain Protein Grd19p Complexed to Phosphatidylinositol-3-phosphate

Cong-Zhao Zhou (1) , Ines Li de La Sierra-Gallay (2) , Sophie Quevillon-Cheruel (1) , Bruno Collinet (1) , Philippe Minard (1) , Karine Blondeau (3) , Gilles Henckes (3) , Robert Aufrère (3) , Nicolas Leulliot (1) , Marc Graille (1) , Isabelle Sorel (1) , Philippe Savarin (2) , Françoise de La Torre (2) , Anne Poupon (2) , Joël Janin (2) , Herman van Tilbeurgh (1)

1 IBBMC - Institut de biochimie et biophysique moléculaire et cellulaire
2 LEBS - Laboratoire d'enzymologie et biochimie structurales
3 IGM - Institut de génétique et microbiologie [Orsay]

Phox homology (PX) domains have been recently identified in a number of different proteins and are involved in various cellular functions such as vacuolar targeting and membrane protein trafficking. It was shown that these modules of about 130 amino acids specifically binding to phosphoinositides and that this interaction is crucial for their cellular function. The yeast genome contains 17 PX domain proteins. One of these, Grd19p, is involved in the localization of the late Golgi membrane proteins DPAP A and Kex2p. Grd19p consists of the PX domain with 30 extra residues at the N-terminal and is homologous to the functionally characterized human sorting nexin protein SNX3. We determined the 2.0 Å crystal structure of Grd19p in the free form and in complex with D-myo-phosphatidylinositol 3-phosphate (diC 4 PtdIns(3)P), representing the first case of both free and ligand-bound conformations of the same PX module. The ligand occupies a well defined positively charged binding pocket at the interface between the ␤-sheet and ␣-helical parts of the molecule. The structure of the free and bound protein are globally similar but show some significant differences in a region containing a polyproline peptide and a putative membrane attachment site.

Domaines: Biologie structurale [q-bio.BM]

Cong-Zhao Zhou, Ines Li de La Sierra-Gallay, Sophie Quevillon-Cheruel, Bruno Collinet, Philippe Minard, et al.. Crystal Structure of the Yeast Phox Homology (PX) Domain Protein Grd19p Complexed to Phosphatidylinositol-3-phosphate. Journal of Biological Chemistry, 2003, 278 (50), pp.50371 - 50376. ⟨10.1074/jbc.m304392200⟩. ⟨hal-03299367⟩