1. Structure of human phosphatidylcholine transfer protein in complex with its ligand
- Author
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Diana S. Agate, Steven L. Roderick, Matt W. Vetting, Kanagalaghatta R. Rajashankar, Wayne W. Chan, Laurence R. Olsen, and David E. Cohen
- Subjects
Models, Molecular ,Conformational change ,Stereochemistry ,Phospholipid ,STARD3 ,Phosphatidylethanolamine Binding Protein ,STARD4 ,Crystallography, X-Ray ,Ligands ,Biochemistry ,Androgen-Binding Protein ,Protein Structure, Secondary ,chemistry.chemical_compound ,Structural Biology ,Amphiphile ,Genetics ,Humans ,Phospholipid Transfer Proteins ,Binding Sites ,Ligand ,Phosphatidylcholine transfer protein ,Protein Structure, Tertiary ,chemistry ,Mutation ,Helix ,Phosphatidylcholines ,lipids (amino acids, peptides, and proteins) ,Carrier Proteins ,Protein Binding - 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.
- Published
- 2002
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