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 re...

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Bibliographic Details
Published in:	Nature structural biology Vol. 9; no. 7; pp. 507 - 511
Main Authors:	Roderick, Steven L, Cohen, David E, Chan, Wayne W, Agate, Diana S, Olsen, Laurence R, Vetting, Matt W, Rajashankar, K.R
Format:	Journal Article
Language:	English
Published:	United States 01-07-2002
Subjects:	Androgen-Binding Protein Binding Sites Carrier Proteins - chemistry Carrier Proteins - genetics Carrier Proteins - metabolism Crystallography, X-Ray Humans Ligands Models, Molecular Mutation - genetics Phosphatidylcholines - chemistry Phosphatidylcholines - metabolism Phosphatidylethanolamine Binding Protein Phospholipid Transfer Proteins Protein Binding Protein Structure, Secondary Protein Structure, Tertiary
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Summary:	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-π 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 Ω-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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1072-8368 2331-365X
DOI:	10.1038/nsb812