1IM3

Crystal Structure of the human cytomegalovirus protein US2 bound to the MHC class I molecule HLA-A2/tax


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 

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This is version 1.3 of the entry. See complete history


Literature

Antigen presentation subverted: Structure of the human cytomegalovirus protein US2 bound to the class I molecule HLA-A2.

Gewurz, B.E.Gaudet, R.Tortorella, D.Wang, E.W.Ploegh, H.L.Wiley, D.C.

(2001) Proc Natl Acad Sci U S A 98: 6794-6799

  • DOI: https://doi.org/10.1073/pnas.121172898
  • Primary Citation of Related Structures:  
    1IM3

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HLA CLASS I HISTOCOMPATIBILITY ANTIGEN, A-2 ALPHA CHAIN
A, E, I, M
275Homo sapiensMutation(s): 0 
Gene Names: HLA-A2
UniProt & NIH Common Fund Data Resources
Find proteins for P04439 (Homo sapiens)
Explore P04439 
Go to UniProtKB:  P04439
PHAROS:  P04439
GTEx:  ENSG00000206503 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04439
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
beta-2-microglobulin
B, F, J, N
100Homo sapiensMutation(s): 0 
Gene Names: Beta 2-microglobulin
UniProt & NIH Common Fund Data Resources
Find proteins for P61769 (Homo sapiens)
Explore P61769 
Go to UniProtKB:  P61769
PHAROS:  P61769
GTEx:  ENSG00000166710 
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UniProt GroupP61769
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Human T-cell lymphotropic virus type 1 Tax peptide
C, G, K, O
9N/AMutation(s): 0 
UniProt
Find proteins for P14079 (Human T-cell leukemia virus 1 (isolate Caribbea HS-35 subtype A))
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UniProt GroupP14079
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
cytomegalovirus protein US2
D, H, L, P
95Human betaherpesvirus 5Mutation(s): 0 
Gene Names: US2
UniProt
Find proteins for P09713 (Human cytomegalovirus (strain AD169))
Explore P09713 
Go to UniProtKB:  P09713
Entity Groups  
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UniProt GroupP09713
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 95.48α = 109.02
b = 96.7β = 109.46
c = 99.54γ = 107.93
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-06-06
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-16
    Changes: Data collection, Database references, Refinement description