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Structure of human phosphatidylcholine transfer protein in complex with its ligand

Nature Structural Biology volume 9, pages 507–511 (2002)Cite this article

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–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.

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Figure 1: Overall structure of human PC-TP.
Figure 2: Structural comparison of START domains.
Figure 3: The PtdCho-binding pocket.

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Acknowledgements

This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the Alexandrine and Alexander L. Sinsheimer Fund. W.W.C. is the recipient of an American Gastroenterological Association Summer Student Fellowship. M.W.V. was supported by a grant from the National Institute of Allergy and Infectious Diseases. We would like to acknowledge the assistance of M. Sullivan at NSLS beamline X9A of the Brookhaven National Laboratories.

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Author notes

  1. K.R. Rajashankar

    Present address: Argonne National Laboratory, APS/SGX-CAT, Building 438/A002 9700, South Cass Avenue, Argonne, Illinois, 60439, USA

Authors and Affiliations

  1. Department of Biochemistry, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, 10461, New York, USA

    Steven L. Roderick, Diana S. Agate, Laurence R. Olsen, Matt W. Vetting & David E. Cohen

  2. Department of Medicine, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, 10461, New York, USA

    Wayne W. Chan & David E. Cohen

  3. Brookhaven National Laboratory, National Synchrotron Light Source, Building 725A-X9, Upton, 11973, New York, USA

    K.R. Rajashankar

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Correspondence to Steven L. Roderick or David E. Cohen.

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Roderick, S., Chan, W., Agate, D. et al. Structure of human phosphatidylcholine transfer protein in complex with its ligand. Nat Struct Mol Biol 9, 507–511 (2002). https://doi.org/10.1038/nsb812

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