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PDBsum entry 1yxk
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Lipid binding protein
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PDB id
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1yxk
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References listed in PDB file
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Key reference
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Title
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Crystal structure of human lectin-Like, Oxidized low-Density lipoprotein receptor 1 ligand binding domain and its ligand recognition mode to oxldl.
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Authors
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I.Ohki,
T.Ishigaki,
T.Oyama,
S.Matsunaga,
Q.Xie,
M.Ohnishi-Kameyama,
T.Murata,
D.Tsuchiya,
S.Machida,
K.Morikawa,
S.Tate.
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Ref.
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Structure, 2005,
13,
905-917.
[DOI no: ]
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PubMed id
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Abstract
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Lectin-like, oxidized low-density lipoprotein (LDL) receptor 1, LOX-1, is the
major receptor for oxidized LDL (OxLDL) in endothelial cells. We have determined
the crystal structure of the ligand binding domain of LOX-1, with a short stalk
region connecting the domain to the membrane-spanning region, as a homodimer
linked by an interchain disulfide bond. In vivo assays with LOX-1 mutants
revealed that the "basic spine," consisting of linearly aligned
arginine residues spanning over the dimer surface, is responsible for ligand
binding. Single amino acid substitution in the dimer interface caused a severe
reduction in LOX-1 binding activity, suggesting that the correct dimer
arrangement is crucial for binding to OxLDL. Based on the LDL model structure,
possible binding modes of LOX-1 to OxLDL are proposed.
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Figure 5.
Figure 5. The Empty Cavity in the Dimer Interface of LOX-1
(A) Empty cavity located at the dimer interface in the
LOX-1 disulfide-lined dimer structure. The surrounding residues
of the cavity are shown as bold lines.
(B) Possible effect
of the W150A mutation on the basic spine structure on the LOX-1
ligand recognition surface. The W150A mutation may resize the
empty cavity in the dimer interface, which subsequently
disarranges the dimer, resulting in the disruption of the basic
spine structure. The disrupted basic spine structure should lead
to severe reduction of the binding ability to ligands.
(C)
A plausible representation of the entire structure of LOX-1 at
the cell surface, based on the crystal structure for CTLD and
the model structure for the NECK. Modeling was performed by
using the myosin heavy chain coiled-coil structure, which shows
a high level of sequence homology to the NECK region.
(D)
Scale comparison between the the OxLDL particle and LOX-1 dimer.
The assembled structure of LOX-1 is drawn according to the
results of cell biology studies that showed LOX-1 to exist as a
hexamer on the cell surface (Xie et al., 2004). The diameter of
OxLDL was estimated from cryoelectron microscopic observation of
the LDL particle (Segrest et al., 2001). In this comparison, it
is assumed that no significant structural alterations are
induced by oxidation to the LDL particle.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2005,
13,
905-917)
copyright 2005.
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