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PDBsum entry 3d2u
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Immune system
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PDB id
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3d2u
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Contents |
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281 a.a.
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99 a.a.
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182 a.a.
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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 ul18, A peptide-Binding viral mhc mimic, Bound to a host inhibitory receptor.
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Authors
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Z.Yang,
P.J.Bjorkman.
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Ref.
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Proc Natl Acad Sci U S A, 2008,
105,
10095-10100.
[DOI no: ]
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PubMed id
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Abstract
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UL18 is a human cytomegalovirus class I MHC (MHCI) homolog that binds the host
inhibitory receptor LIR-1 and the only known viral MHC homolog that presents
peptides. The 2.2-A structure of a LIR-1/UL18/peptide complex reveals increased
contacts and optimal surface complementarity in the LIR-1/UL18 interface
compared with LIR/MHCI interfaces, resulting in a >1,000-fold higher
affinity. Despite sharing only approximately 25% sequence identity, UL18's
structure and peptide binding are surprisingly similar to host MHCI. The crystal
structure suggests that most of the UL18 surface, except where LIR-1 and the
host-derived light chain bind, is covered by carbohydrates attached to 13
potential N-glycosylation sites, thereby preventing access to bound peptide and
association with most MHCI-binding proteins. The LIR-1/UL18 structure
demonstrates how a viral protein evolves from its host ancestor to impede
unwanted interactions while preserving and improving its receptor-binding site.
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Figure 4.
Surface representations of LIR proteins and their binding
partners. Contact surfaces (≤4.0 Å) are highlighted in
yellow. (A) UL18, UL18/LIR-1, and LIR-1. An asterisk marks the
position of a LIR-1 loop (residues 148–154) that is disordered
in the UL18/LIR-1 complex structure. (B) HLA-A2, HLA-A2/LIR-1,
and LIR-1 (PDB ID code 1P7Q). (C) HLA-G, HLA-G/LIR-2, and LIR-2
(PDB ID code 2DYP).
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Figure 5.
Interaction sites for potential binding partners
highlighted on a fully glycosylated UL18 model. (A)
Space-filling representation of the UL18/LIR-1 complex (UL18 in
magenta, β2m in slate, peptide in light green, LIR-1 in cyan)
with a complex carbohydrate model (yellow) attached to each of
the 13 potential N-glycosylation sites. The single predicted
O-glycosylation site (residue 281) within the UL18 ectodomain is
indicated by an orange sphere. Two to three additional
O-glycosylation sites are predicted in the region C-terminal to
the UL18 ectodomain fragment that was crystallized, but these
sites would be distant from the binding sites for all potential
UL18 binding partners. The UL18 counterparts of the approximate
binding sites on a class I MHC molecule for a TCR or KIR are
indicated by arrows. (B) Top view of the fully glycosylated UL18
peptide binding platform. (C) Potential US2 binding site (dark
green) on fully glycosylated UL18. (D) Potential CD8 binding
site (dark green) on fully glycosylated UL18. An enlarged view
of the CD8-binding loop in the class I MHC α3 domain (gray) is
shown with the counterpart UL18 loop (magenta).
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