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Title: Crystal Structure of the Murine Cytomegalovirus MHC-I Homolog m144

Abstract

Large DNA viruses of the herpesvirus family produce proteins that mimic host MHC-I molecules as part of their immunoevasive strategy. The m144 glycoprotein, expressed by murine cytomegalovirus, is thought to be an MHC-I homolog whose expression prolongs viral survival in vivo by preventing natural killer cell activation. To explore the structural basis of this m144 function, we have determined the three-dimensional structure of an m144/{beta}2-microglobulin ({beta}2m) complex at 1.9 {angstrom} resolution. This structure reveals the canonical features of MHC-I molecules including readily identifiable {alpha}1, {alpha}2, and {alpha}3 domains. A unique disulfide bond links the {alpha}1 helix to the {beta}-sheet floor, explaining the known thermal stability of m144. Close juxtaposition of the {alpha}1 and {alpha}2 helices and the lack of critical residues that normally contribute to anchoring the peptide N and C termini eliminates peptide binding. A region of 13 amino acid residues, corresponding to the amino-terminal portion of the {alpha}2 helix, is missing in the electron density map, suggesting an area of structural flexibility that may be involved in ligand binding.

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930212
Report Number(s):
BNL-80875-2008-JA
Journal ID: ISSN 0022-2836; JMOBAK; TRN: US200822%%1391
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Molecular Biology; Journal Volume: 358
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; AMINO ACIDS; CRYSTAL STRUCTURE; DISULFIDES; DNA; ELECTRON DENSITY; FASTENING; FLEXIBILITY; HOST; IN VIVO; LIGANDS; MOLECULES; NATURAL KILLER CELLS; PEPTIDES; PROGRAMMING LANGUAGES; PROTEINS; RESIDUES; RESOLUTION; STABILITY; VIRUSES; national synchrotron light source

Citation Formats

Natarajan,K., Hicks, A., Mans, J., Robinson, H., Guan, R., Mariuzza, R., and Margulies, D. Crystal Structure of the Murine Cytomegalovirus MHC-I Homolog m144. United States: N. p., 2006. Web. doi:10.1016/j.jmb.2006.01.068.
Natarajan,K., Hicks, A., Mans, J., Robinson, H., Guan, R., Mariuzza, R., & Margulies, D. Crystal Structure of the Murine Cytomegalovirus MHC-I Homolog m144. United States. doi:10.1016/j.jmb.2006.01.068.
Natarajan,K., Hicks, A., Mans, J., Robinson, H., Guan, R., Mariuzza, R., and Margulies, D. Sun . "Crystal Structure of the Murine Cytomegalovirus MHC-I Homolog m144". United States. doi:10.1016/j.jmb.2006.01.068.
@article{osti_930212,
title = {Crystal Structure of the Murine Cytomegalovirus MHC-I Homolog m144},
author = {Natarajan,K. and Hicks, A. and Mans, J. and Robinson, H. and Guan, R. and Mariuzza, R. and Margulies, D.},
abstractNote = {Large DNA viruses of the herpesvirus family produce proteins that mimic host MHC-I molecules as part of their immunoevasive strategy. The m144 glycoprotein, expressed by murine cytomegalovirus, is thought to be an MHC-I homolog whose expression prolongs viral survival in vivo by preventing natural killer cell activation. To explore the structural basis of this m144 function, we have determined the three-dimensional structure of an m144/{beta}2-microglobulin ({beta}2m) complex at 1.9 {angstrom} resolution. This structure reveals the canonical features of MHC-I molecules including readily identifiable {alpha}1, {alpha}2, and {alpha}3 domains. A unique disulfide bond links the {alpha}1 helix to the {beta}-sheet floor, explaining the known thermal stability of m144. Close juxtaposition of the {alpha}1 and {alpha}2 helices and the lack of critical residues that normally contribute to anchoring the peptide N and C termini eliminates peptide binding. A region of 13 amino acid residues, corresponding to the amino-terminal portion of the {alpha}2 helix, is missing in the electron density map, suggesting an area of structural flexibility that may be involved in ligand binding.},
doi = {10.1016/j.jmb.2006.01.068},
journal = {Journal of Molecular Biology},
number = ,
volume = 358,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}