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

11 Citations (Scopus)

Abstract

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
Volume289
Issue number34
DOIs
Publication statusPublished - 2014

Cite this

@article{8038078810a948759f25fe24b3ccc7fc,
title = "The structure of the cytomegalovirus-encoded m04 glycoprotein, a prototypical member of the m02 family of immunoevasins",
abstract = "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.",
author = "Richard Berry and Vivian, {Julian P} and Deuss, {Felix A} and Balaji, {Gautham Raj} and Saunders, {Philippa M} and Jie Lin and Dene Littler and Brooks, {Andrew G} and Jamie Rossjohn",
year = "2014",
doi = "10.1074/jbc.M114.584128",
language = "English",
volume = "289",
pages = "23753 -- 23763",
journal = "Journal of Biological Chemistry",
issn = "1083-351X",
publisher = "American Society for Biochemistry and Molecular Biology",
number = "34",

}

The structure of the cytomegalovirus-encoded m04 glycoprotein, a prototypical member of the m02 family of immunoevasins. / Berry, Richard; Vivian, Julian P; Deuss, Felix A; Balaji, Gautham Raj; Saunders, Philippa M; Lin, Jie; Littler, Dene; Brooks, Andrew G; Rossjohn, Jamie.

In: Journal of Biological Chemistry, Vol. 289, No. 34, 2014, p. 23753 - 23763.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The structure of the cytomegalovirus-encoded m04 glycoprotein, a prototypical member of the m02 family of immunoevasins

AU - Berry, Richard

AU - Vivian, Julian P

AU - Deuss, Felix A

AU - Balaji, Gautham Raj

AU - Saunders, Philippa M

AU - Lin, Jie

AU - Littler, Dene

AU - Brooks, Andrew G

AU - Rossjohn, Jamie

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.jbc.org/content/289/34/23753.full.pdf+html

U2 - 10.1074/jbc.M114.584128

DO - 10.1074/jbc.M114.584128

M3 - Article

VL - 289

SP - 23753

EP - 23763

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 1083-351X

IS - 34

ER -