title: Structure of human phosphatidylcholine transfer protein in complex with its ligand.
abstract: Phosphatidylcholines (PtdChos) comprise the most common phospholipid class in eukaryotic cells. In mammalian cells, these insoluble molecules are transferred between membranes by a highly specific phosphatidylcholine transfer protein (PC-TP) belonging to the steroidogenic acute regulatory protein related transfer (START) domain superfamily of hydrophobic ligand-binding proteins. The crystal structures of human PC-TP in complex with dilinoleoyl-PtdCho or palmitoyl-linoleoyl-PtdCho reveal that a single well-ordered PtdCho molecule occupies a centrally located tunnel. The positively charged choline headgroup of the lipid engages in cation-pi interactions within a cage formed by the faces of three aromatic residues. These binding determinants and those for the phosphoryl group may be exposed to the lipid headgroup at the membrane-water interface by a conformational change involving the amphipathic C-terminal helix and an Omega-loop. The structures presented here provide a basis for rationalizing the specificity of PC-TP for PtdCho and may identify common features used by START proteins to bind their hydrophobic ligands.
authors.affiliation: Department of Biochemistry, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA. roderick@aecom.yu.edu
authors.forename: Steven L
authors.initials: SL
authors.lastname: Roderick
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Chan
authors.forename: Diana S
authors.initials: DS
authors.lastname: Agate
authors.forename: Laurence R
authors.initials: LR
authors.lastname: Olsen
authors.forename: Matt W
authors.initials: MW
authors.lastname: Vetting
authors.forename: K R
authors.initials: KR
authors.lastname: Rajashankar
authors.forename: David E
authors.initials: DE
authors.lastname: Cohen
mesh_terms: D000727:Androgen-Binding Protein; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000378:metabolism*; D049488:Phosphatidylethanolamine Binding Protein; D049294:Phospholipid Transfer Proteins; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D000727:Androgen-Binding Protein; D002352:Carrier Proteins; D008024:Ligands; C511482:PEBP1 protein, human; D010713:Phosphatidylcholines; D049488:Phosphatidylethanolamine Binding Protein; D049294:Phospholipid Transfer Proteins