Structure of human phosphatidylcholine transfer protein in complex with its ligand

Steven L. Roderick, Wayne W. Chan, Diana S. Agate, Laurence R. Olsen, Matt W. Vetting, K. R. Rajashankar, David E. Cohen

Research output: Contribution to journalArticle

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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 head group 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.

Original languageEnglish (US)
Pages (from-to)507-511
Number of pages5
JournalNature Structural Biology
Volume9
Issue number7
DOIs
StatePublished - 2002

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Phospholipid Transfer Proteins
Ligands
Membranes
Lipids
Molecules
Eukaryotic Cells
Choline
Phosphatidylcholines
Cations
Phospholipids
Tunnels
Carrier Proteins
Crystal structure
Cells
Water
Proteins
steroidogenic acute regulatory protein

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Genetics

Cite this

Roderick, S. L., Chan, W. W., Agate, D. S., Olsen, L. R., Vetting, M. W., Rajashankar, K. R., & Cohen, D. E. (2002). Structure of human phosphatidylcholine transfer protein in complex with its ligand. Nature Structural Biology, 9(7), 507-511. https://doi.org/10.1038/nsb812

Structure of human phosphatidylcholine transfer protein in complex with its ligand. / Roderick, Steven L.; Chan, Wayne W.; Agate, Diana S.; Olsen, Laurence R.; Vetting, Matt W.; Rajashankar, K. R.; Cohen, David E.

In: Nature Structural Biology, Vol. 9, No. 7, 2002, p. 507-511.

Research output: Contribution to journalArticle

Roderick, SL, Chan, WW, Agate, DS, Olsen, LR, Vetting, MW, Rajashankar, KR & Cohen, DE 2002, 'Structure of human phosphatidylcholine transfer protein in complex with its ligand', Nature Structural Biology, vol. 9, no. 7, pp. 507-511. https://doi.org/10.1038/nsb812
Roderick SL, Chan WW, Agate DS, Olsen LR, Vetting MW, Rajashankar KR et al. Structure of human phosphatidylcholine transfer protein in complex with its ligand. Nature Structural Biology. 2002;9(7):507-511. https://doi.org/10.1038/nsb812
Roderick, Steven L. ; Chan, Wayne W. ; Agate, Diana S. ; Olsen, Laurence R. ; Vetting, Matt W. ; Rajashankar, K. R. ; Cohen, David E. / Structure of human phosphatidylcholine transfer protein in complex with its ligand. In: Nature Structural Biology. 2002 ; Vol. 9, No. 7. pp. 507-511.
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