Structure of human phosphatidylcholine transfer protein in complex with its ligand.
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.
Roderick
Steven L
SL
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
Chan
Wayne W
WW
Agate
Diana S
DS
Olsen
Laurence R
LR
Vetting
Matt W
MW
Rajashankar
K R
KR
Cohen
David E
DE
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
D000727:Androgen-Binding Protein; D002352:Carrier Proteins; D008024:Ligands; C511482:PEBP1 protein, human; D010713:Phosphatidylcholines; D049488:Phosphatidylethanolamine Binding Protein; D049294:Phospholipid Transfer Proteins