4pn6

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Structure of the Cytomegalovirus-Encoded m04 GlycoproteinStructure of the Cytomegalovirus-Encoded m04 Glycoprotein

Structural highlights

4pn6 is a 2 chain structure with sequence from Muromegalovirus G4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

B3UWV7_MUHV1

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.

References

  1. Berry R, Vivian JP, Deuss FA, Balaji GR, Saunders PM, Lin J, Littler DR, Brooks AG, Rossjohn J. The Structure of the Cytomegalovirus-Encoded m04 Glycoprotein, a Prototypical Member of the m02 Family of Immunoevasins. J Biol Chem. 2014 Jun 30. pii: jbc.M114.584128. PMID:24982419 doi:http://dx.doi.org/10.1074/jbc.M114.584128

4pn6, resolution 3.00Å

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OCA