Structure-function analysis of human [corrected] phosphatidylinositol transfer protein alpha bound to phosphatidylinositol.
作者： Sarah J. Tilley , Alison Skippen , Judith Murray-Rust , Philip M. Swigart , Albert Stewart
DOI: 10.1016/J.STR.2004.01.013
关键词: Phospholipase C 、 Phosphatidylinositol transfer protein 、 Phosphatidylinositol transfer protein, alpha 、 Ligand (biochemistry) 、 Cell biology 、 Lipid bilayer 、 Biology 、 Phosphatidylinositol 、 Protein structure 、 Binding site
摘要: Phosphatidylinositol transfer protein α (PITPα) selectively transports and promotes exchange of phosphatidylinositol (PI) phosphatidylcholine (PC) between lipid bilayers. In higher eukaryotes PITPα is required for cellular functions such as phospholipase C-mediated signaling, regulated exocytosis, secretory vesicle formation. We have determined the crystal structure human bound to its physiological ligand, PI, at 2.95 A resolution. The identifies critical side chains within lipid-headgroup binding pocket that define exquisite specificity PI. Mutational analysis PI in good agreement with structural data allows manipulation functional properties PITPα. Surprisingly, there are no major conformational differences PI- PC-loaded PITPα, despite previous predictions. crystal, PITPα-PI dimeric, two identical dimers asymmetric unit. dimer interface masks precisely sequence we identify contributing membrane interaction. Our represents a soluble, transport-competent form PI-loaded
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