The structure of phosphatidylinositol transfer protein alpha reveals sites for phospholipid binding and membrane association with major implications for its function.
Elucidation of the three-dimensional structure of phosphatidylinositol transfer protein alpha (PI-TPalpha) void of phospholipid revealed a site of membrane association connected to a channel for phospholipid binding. Near the top of the channel specific binding sites for the phosphorylcholine and phosphorylinositol head groups were identified. The structure of this open form suggests a mechanism by which PI-TPalpha preferentially binds PI from a membrane interface. Modeling predicts that upon association of PI-TPalpha with the membrane the inositol moiety of bound PI is accessible from the medium. Upon release from the membrane PI-TPalpha adopts a closed structure with the phospholipid bound fully encapsulated. This structure provides new insights as to how PI-TPalpha may play a role in PI metabolism.
van Tiel
Claudia M
CM
Center for Biomembranes and Lipid Enzymology, Department of Lipid Biochemistry, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
Schouten
Arie
A
Snoek
Gerry T
GT
Gros
Piet
P
Wirtz
Karel W A
KW
D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D002462:Cell Membrane / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry*; D051379:Mice; D008956:Models, Chemical; D008958:Models, Molecular; D049294:Phospholipid Transfer Proteins; D010767:Phosphorylcholine / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats; D029701:Saccharomyces cerevisiae Proteins
D002352:Carrier Proteins; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; C118289:SEC24 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D010767:Phosphorylcholine