PMID- 16452487
OWN - NLM
STAT- MEDLINE
DCOM- 20060523
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 281
IP  - 13
DP  - 2006 Mar 31
TI  - Dissection of the interaction of the human cytomegalovirus-derived US2 protein 
      with major histocompatibility complex class I molecules: prominent role of a 
      single arginine residue in human leukocyte antigen-A2.
PG  - 8950-7
AB  - Human cytomegalovirus encodes several proteins that interfere with expression of 
      major histocompatibility complex (MHC) class I molecules on the surface of 
      infected cells. The unique short protein 2 (US2) binds to many MHC class I 
      allomorphs in the endoplasmic reticulum, preventing cell surface expression of 
      the class I molecule in question. The molecular interactions underlying US2 
      binding to MHC class I molecules and its allele specificity have not been fully 
      clarified. In the present study, we first compared the sequences and the 
      structures of US2 retained versus non-retained human leukocyte antigen (HLA) 
      class I allomorphs to identify MHC residues of potential importance for US2 
      binding. On the basis of this analysis, 18 individual HLA-A2 mutants were 
      generated and the ability of full-length US2 to bind wild-type and mutated HLA-A2 
      complexes was assessed. We demonstrate that Arg181 plays a critical role in 
      US2-mediated inhibition of HLA-A2 cell surface expression. The structural 
      comparison of all known crystal structures of HLA-A2 either alone, or in complex 
      with T cell receptor or the CD8 co-receptor, indicates that binding of US2 to 
      HLA-A2 results in a unique, large conformational change of the side chain of 
      Arg181. However, although the presence of Arg181 seems to be a prerequisite for 
      US2 binding to HLA-A2, it is not sufficient for binding to all MHC class I 
      alleles.
FAU - Thilo, Claudia
AU  - Thilo C
AD  - Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 
      Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden.
FAU - Berglund, Peter
AU  - Berglund P
FAU - Applequist, Steven E
AU  - Applequist SE
FAU - Yewdell, Jonathan W
AU  - Yewdell JW
FAU - Ljunggren, Hans-Gustaf
AU  - Ljunggren HG
FAU - Achour, Adnane
AU  - Achour A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060201
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (US2 protein, Varicellovirus)
RN  - 0 (Viral Envelope Proteins)
RN  - 0 (Wdr83 protein, rat)
RN  - 94ZLA3W45F (Arginine)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Alleles
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Monoclonal/metabolism
MH  - Arginine/chemistry/*metabolism
MH  - Binding Sites
MH  - Cell Line
MH  - Consensus Sequence
MH  - Flow Cytometry
MH  - Fluorescein-5-isothiocyanate
MH  - Fluorescent Dyes
MH  - HLA-A2 Antigen/*chemistry/genetics/*metabolism
MH  - Histocompatibility Antigens Class I/*chemistry/genetics/*metabolism
MH  - Humans
MH  - Hydrogen Bonding
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Protein Binding
MH  - Protein Conformation
MH  - Protein Structure, Secondary
MH  - Sequence Homology, Amino Acid
MH  - Transgenes
MH  - Vaccinia
MH  - Viral Envelope Proteins/*metabolism
EDAT- 2006/02/03 09:00
MHDA- 2006/05/24 09:00
CRDT- 2006/02/03 09:00
PHST- 2006/02/03 09:00 [pubmed]
PHST- 2006/05/24 09:00 [medline]
PHST- 2006/02/03 09:00 [entrez]
AID - S0021-9258(19)56600-5 [pii]
AID - 10.1074/jbc.M507121200 [doi]
PST - ppublish
SO  - J Biol Chem. 2006 Mar 31;281(13):8950-7. doi: 10.1074/jbc.M507121200. Epub 2006 
      Feb 1.