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Structural elements underlying the high binding affinity of human cytomegalovirus UL18 to leukocyte immunoglobulin-like receptor-1
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2007 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 373, no 3, 695-705 p.Article in journal (Refereed) Published
Abstract [en]

Human cytomegalovirus (HCMV) encodes UL18, a major histocompatibility complex (MHC) class I homologue that binds to the leukocyte immunoglobulin-like receptor (LIR)-1 (also called ILT2/CD85j/LILRB1), an inhibitory receptor expressed on myeloid and lymphoid immune cells. The molecular basis underlying the high affinity binding of UL18 to LIR-1, compared to MHC class I molecules (MHC-I), is unclear. Based on a comparative structural analysis of a molecular model of UL18 with the crystal structure of the HLA-A2/LIR-1 complex, we identified three regions in UL18 influencing interaction with LIR-1. Comparison of the relative binding affinities of mutated UL18 proteins to LIR-1 demonstrated the importance of specific residues in each region. Substitution of residues K42/A43 and Q202, localized in the alpha 1 and alpha 3 domains, respectively, reduced binding affinity to LIR-1 nearly by half. The model also suggested the formation of an additional disulfide bridge in the 0 domain of UL18 between residues C240 and C255, not present in MHC-I. Substitution of either cysteine residue prevented association of UL18 to beta(2)m, abolishing binding to LIR-1. All observed differences in binding affinities translated directly into functional consequences in terms of inhibition of IFN-gamma production by T cells, mediated through the UL18-LIR-1 interaction. The larger amount of interacting regions, combined with an increased stability of the alpha 3 and beta(2)m domains allow a higher recognition affinity of UL18 by LIR-1.

Place, publisher, year, edition, pages
2007. Vol. 373, no 3, 695-705 p.
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:sh:diva-14203DOI: 10.1016/j.jmb.2007.08.020ISI: 000250440000015PubMedID: 17869268Scopus ID: 2-s2.0-34748843922OAI: oai:DiVA.org:sh-14203DiVA: diva2:467941
Available from: 2011-12-20 Created: 2011-12-19 Last updated: 2016-01-08Bibliographically approved

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Berndt, Kurt D.
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CiteExportLink to record
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Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
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  • de-DE
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