4pn6

Publication Abstract from PubMed

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.

The Structure of the Cytomegalovirus-Encoded m04 Glycoprotein, a Prototypical Member of the m02 Family of Immunoevasins.,Berry R, Vivian JP, Deuss FA, Balaji GR, Saunders PM, Lin J, Littler DR, Brooks AG, Rossjohn J J Biol Chem. 2014 Jun 30. pii: jbc.M114.584128. PMID:24982419^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.