The structure of the cytomegalovirus-encoded m04 glycoprotein, a prototypical member of the m02 family of immunoevasins

Richard Berry, Julian P Vivian, Felix A Deuss, Gautham Raj Balaji, Philippa M Saunders, Jie Lin, Dene Littler, Andrew G Brooks, Jamie Rossjohn

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)


The ability of cytomegaloviruses (CMV) to evade the host s immune system is dependent on the expression of a wide array of glycoproteins, many of which interfere with natural killer (NK) cell function. In murine CMV, two large protein families mediate this immune-evasive function. While it is established that the m145 family members mimic the structure of major histocompatibility complex (MHC)-I molecules, the structure of the m02 family remains unknown. The most extensively studied m02 family member is m04, a glycoprotein that escorts newly assembled MHC-I molecules to the cell surface, presumably to avoid missing-self recognition. Here we report the crystal structure of the m04 ectodomain, thereby providing insight into this large immunoevasin family. m04 adopted a beta-sandwich immunoglobulin variable (Ig-V) like fold, despite sharing very little sequence identity with the Ig-V superfamily. In addition to the Ig-V core, m04 possesses several unique structural features that included an unusual beta-strand topology, a number of extended loops and a prominent alpha-helix. The m04 interior was packed by a myriad of hydrophobic residues that form distinct clusters around two conserved tryptophan residues. This hydrophobic core was well conserved throughout the m02 family, thereby indicating that MCMV encodes a number of Ig-V like molecules. We show that m04 binds a range of MHC-I molecules with low affinity in a peptide-independent manner. Accordingly the structure of m04, which represents the first example of an MCMV encoded Ig-V fold, provides a basis for understanding the structure and function of this enigmatic and large family of immunoevasins.
Original languageEnglish
Pages (from-to)23753 - 23763
Number of pages11
JournalJournal of Biological Chemistry
Issue number34
Publication statusPublished - 2014

Cite this