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PDBsum entry 1ln1
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Lipid binding protein
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PDB id
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1ln1
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structure of human phosphatidylcholine transfer protein in complex with its ligand.
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Authors
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S.L.Roderick,
W.W.Chan,
D.S.Agate,
L.R.Olsen,
M.W.Vetting,
K.R.Rajashankar,
D.E.Cohen.
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Ref.
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Nat Struct Biol, 2002,
9,
507-511.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 2.
Figure 2. Structural comparison of START domains. Stereo view
superposition of the C  traces
of PC-TP (blue) and MLN64 (gray) based on 126 paired C positions.
The most similar regions are the  -strands
of the central -sheet
that form the floor of the lipid binding tunnel, whereas the
most significant differences include the positioning of loop
 1
and the C-terminal helix.
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Figure 3.
Figure 3. The PtdCho-binding pocket. a, Views of the solvent
accessible volume of the binding pocket, separated by a 90°
rotation. b, Stereo view of the interactions of PC-TP with the
glycerol-3-phosphorylcholine moiety of PLPC (yellow). The
structure of DLPC from the PC-TPâDLPC complex is superimposed
(gray). c, Stereo view of the interactions of the
phosphorylcholine quaternary amine with PC-TP (yellow) and the
trimethyllysine residue of the histone H3 tail with HP1 (ref.
24) (gray). The residues of the three-walled aromatic cage of
PC-TP are labeled.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2002,
9,
507-511)
copyright 2002.
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