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PDBsum entry 1im3
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Viral protein/immune system
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PDB id
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1im3
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Contents |
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275 a.a.
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100 a.a.
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95 a.a.
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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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Antigen presentation subverted: structure of the human cytomegalovirus protein us2 bound to the class i molecule hla-A2.
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Authors
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B.E.Gewurz,
R.Gaudet,
D.Tortorella,
E.W.Wang,
H.L.Ploegh,
D.C.Wiley.
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Ref.
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Proc Natl Acad Sci U S A, 2001,
98,
6794-6799.
[DOI no: ]
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PubMed id
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Abstract
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Many persistent viruses have evolved the ability to subvert MHC class I antigen
presentation. Indeed, human cytomegalovirus (HCMV) encodes at least four
proteins that down-regulate cell-surface expression of class I. The HCMV unique
short (US)2 glycoprotein binds newly synthesized class I molecules within the
endoplasmic reticulum (ER) and subsequently targets them for proteasomal
degradation. We report the crystal structure of US2 bound to the HLA-A2/Tax
peptide complex. US2 associates with HLA-A2 at the junction of the
peptide-binding region and the alpha3 domain, a novel binding surface on class I
that allows US2 to bind independently of peptide sequence. Mutation of class I
heavy chains confirms the importance of this binding site in vivo. Available
data on class I-ER chaperone interactions indicate that chaperones would not
impede US2 binding. Unexpectedly, the US2 ER-luminal domain forms an Ig-like
fold. A US2 structure-based sequence alignment reveals that seven HCMV proteins,
at least three of which function in immune evasion, share the same fold as US2.
The structure allows design of further experiments to determine how US2 targets
class I molecules for degradation.
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Figure 3.
Fig. 3. US2 binds remotely from peptide-loading proteins.
The positions of mutations (blue) that alter interactions
between class I molecules and the peptide-loading machinery are
shown relative to the US2 binding site on HLA-A2 (magenta). The
HLA-A2 N-linked glycan attachment site, asparagine 86, is also
shown in blue. US2 residues that contact HLA-A2 are yellow.
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Figure 4.
Fig. 4. Protein ligands for class I molecules interact
with different surfaces. Superposition of class I/receptor
complexes for which the structure is known reveals that the five
class I ligand types bind at distinct locations. Class I
interaction surfaces are colored according to each ligand: US2
(magenta), Ly49A (green), B7 TCR (blue), KIR2DL1 (red), CD8  (cyan).
Equivalent C atoms for
class I heavy chain were used to generate pairwise
superpositions. HLA-A2 heavy chain (yellow),  [2]-microglobulin
(gray), US2 (magenta), Tax peptide (green).
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Secondary reference #1
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Title
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Human cytomegalovirus us2 endoplasmic reticulum-Lumenal domain dictates association with major histocompatibility complex class i in a locus-Specific manner.
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Authors
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B.E.Gewurz,
E.W.Wang,
D.Tortorella,
D.J.Schust,
H.L.Ploegh.
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Ref.
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J Virol, 2001,
75,
5197-5204.
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PubMed id
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Secondary reference #2
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Title
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The structure and stability of an hla-A0201/Octameric tax peptide complex with an empty conserved peptide-N-Terminal binding site.
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Authors
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A.R.Khan,
B.M.Baker,
P.Ghosh,
W.E.Biddison,
D.C.Wiley.
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Ref.
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J Immunol, 2000,
164,
6398-6405.
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PubMed id
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Secondary reference #3
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Title
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Sec61-Mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction.
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Authors
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E.J.Wiertz,
D.Tortorella,
M.Bogyo,
J.Yu,
W.Mothes,
T.R.Jones,
T.A.Rapoport,
H.L.Ploegh.
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Ref.
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Nature, 1996,
384,
432-438.
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PubMed id
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