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PDBsum entry 1ozn
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Signaling protein
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PDB id
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1ozn
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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 the nogo receptor ectodomain: a recognition module implicated in myelin inhibition.
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Authors
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X.L.He,
J.F.Bazan,
G.Mcdermott,
J.B.Park,
K.Wang,
M.Tessier-Lavigne,
Z.He,
K.C.Garcia.
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Ref.
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Neuron, 2003,
38,
177-185.
[DOI no: ]
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PubMed id
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Abstract
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Failure of axon regeneration in the adult mammalian central nervous system (CNS)
is at least partly due to inhibitory molecules associated with myelin. Recent
studies suggest that an axon surface protein, the Nogo receptor (NgR), may play
a role in this process through an unprecedented degree of crossreactivity with
myelin-associated inhibitory ligands. Here, we report the 1.5 A crystal
structure and functional characterization of a soluble extracellular domain of
the human Nogo receptor. Nogo receptor adopts a leucine-rich repeat (LRR) module
whose concave exterior surface contains a broad region of evolutionarily
conserved patches of aromatic residues, possibly suggestive of degenerate ligand
binding sites. A deep cleft at the C-terminal base of the LRR may play a role in
NgR association with the p75 coreceptor. These results now provide a detailed
framework for focused structure-function studies aimed at assessing the
physiological relevance of NgR-mediated protein-protein interactions to axon
regeneration inhibition.
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Figure 2.
Figure 2. The Structure of the Nogo Receptor Ligand Binding
Domain(A) Side view. The N-terminal cap domain (LRRNT) is
colored in purple, the leucine-rich repeats (LRR) are in cyan,
and the C-terminal cap (LRRCT) domain is in pink. The
high-mannose Asn-linked glycosylation sites are depicted as
bonds in yellow. The central Phe residues of the “spine” are
depicted as bonds in orange.(B) SIGMAA-weighted 2Fo − Fc
electron density contoured at 1.5σ, showing the spine of the
structure formed by a line of phenylalanine residues.(C) Face-on
view into the concave belly formed by the leucine-rich
repeats.(D) Structural superposition of NgR with the structure
of platelet glycoprotein Ibα, showing a conserved β finger
aside the concave binding face. To the right are the
superpositions showing the similarities and differences between
the LRRNT and LRRCT; note NgR does not contain the β switch
that glycoprotein Ibα uses for ligand capture.
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Figure 4.
Figure 4. Surface Patches within the Concave Face of NgR(A)
Space-filling model of the concave face showing the two surface
clusters enriched in aromatic side chains that are coincident
with the conservation analysis, and a very prominent acidic
cavity situated at the periphery of the groove that likely
mediates specificity contacts through hydrogen bonding (Trp,
Phe, and Tyr in green; His in purple; acidic residues in
yellow).(B) Hydrophobic patch #1 on the upper side of the
concave surface, centered at Trp87, Phe63, and Ile85.(C) The
acidic patch. Three aspartic acid side chains surround Ser113,
forming a depressed acidic region.(D) Hydrophobic patch #2 on
the lower side of the concave surface, centered at Phe184 and
Leu208.(E) The hydrophobic cavity located at the LRRCT
domain.(F) Crystallographic interaction utilizing the LRRCT
hydrophobic cavity.
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The above figures are
reprinted
by permission from Cell Press:
Neuron
(2003,
38,
177-185)
copyright 2003.
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