Structural Basis of Mouse Cytomegalovirus M152/gp40 Interaction with RAE1γ Reveals a Paradigm for MHC/MHC Interaction in Immune Evasion

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2012 Nov 22

PMID 23169621

Citations 19

Authors

Rui Wang

Kannan Natarajan

Maria Jamela R Revilleza

Lisa F Boyd

Li Zhi

Huaying Zhao

Howard Robinson

David H Margulies

Affiliations

Soon will be listed here.

Abstract

Natural killer (NK) cells are activated by engagement of the NKG2D receptor with ligands on target cells stressed by infection or tumorigenesis. Several human and rodent cytomegalovirus (CMV) immunoevasins down-regulate surface expression of NKG2D ligands. The mouse CMV MHC class I (MHC-I)-like m152/gp40 glycoprotein down-regulates retinoic acid early inducible-1 (RAE1) NKG2D ligands as well as host MHC-I. Here we describe the crystal structure of an m152/RAE1γ complex and confirm the intermolecular contacts by mutagenesis. m152 interacts in a pincer-like manner with two sites on the α1 and α2 helices of RAE1 reminiscent of the NKG2D interaction with RAE1. This structure of an MHC-I-like immunoevasin/MHC-I-like ligand complex explains the binding specificity of m152 for RAE1 and allows modeling of the interaction of m152 with classical MHC-I and of related viral immunoevasins.

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References

. The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr. 1994; 50(Pt 5):760-3. DOI: 10.1107/S0907444994003112. View

Li P, McDermott G, Strong R . Crystal structures of RAE-1beta and its complex with the activating immunoreceptor NKG2D. Immunity. 2002; 16(1):77-86. DOI: 10.1016/s1074-7613(02)00258-3. View

Zwart W, Griekspoor A, Kuijl C, Marsman M, van Rheenen J, Janssen H . Spatial separation of HLA-DM/HLA-DR interactions within MIIC and phagosome-induced immune escape. Immunity. 2005; 22(2):221-33. DOI: 10.1016/j.immuni.2005.01.006. View

Svitel J, Balbo A, Mariuzza R, Gonzales N, Schuck P . Combined affinity and rate constant distributions of ligand populations from experimental surface binding kinetics and equilibria. Biophys J. 2003; 84(6):4062-77. PMC: 1302986. DOI: 10.1016/S0006-3495(03)75132-7. View

de Kruijf E, Sajet A, van Nes J, Putter H, Smit V, Eagle R . NKG2D ligand tumor expression and association with clinical outcome in early breast cancer patients: an observational study. BMC Cancer. 2012; 12:24. PMC: 3292504. DOI: 10.1186/1471-2407-12-24. View

Wang J, Whitman M, Natarajan K, Tormo J, Mariuzza R, Margulies D . Binding of the natural killer cell inhibitory receptor Ly49A to its major histocompatibility complex class I ligand. Crucial contacts include both H-2Dd AND beta 2-microglobulin. J Biol Chem. 2001; 277(2):1433-42. DOI: 10.1074/jbc.M110316200. View

Lodoen M, Lanier L . Viral modulation of NK cell immunity. Nat Rev Microbiol. 2004; 3(1):59-69. DOI: 10.1038/nrmicro1066. View

Liljedahl M, Kuwana T, Jackson M, Peterson P, Karlsson L . HLA-DO is a lysosomal resident which requires association with HLA-DM for efficient intracellular transport. EMBO J. 1996; 15(18):4817-24. PMC: 452218. View

Lanier L . Evolutionary struggles between NK cells and viruses. Nat Rev Immunol. 2008; 8(4):259-68. PMC: 2584366. DOI: 10.1038/nri2276. View

10.

Adams P, Afonine P, Bunkoczi G, Chen V, Davis I, Echols N . PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 2):213-21. PMC: 2815670. DOI: 10.1107/S0907444909052925. View

11.

Carayannopoulos L, Naidenko O, Fremont D, Yokoyama W . Cutting edge: murine UL16-binding protein-like transcript 1: a newly described transcript encoding a high-affinity ligand for murine NKG2D. J Immunol. 2002; 169(8):4079-83. DOI: 10.4049/jimmunol.169.8.4079. View

12.

Radaev S, Sun P . Structure and function of natural killer cell surface receptors. Annu Rev Biophys Biomol Struct. 2002; 32:93-114. DOI: 10.1146/annurev.biophys.32.110601.142347. View

13.

Steinle A, Li P, Morris D, Groh V, Lanier L, Strong R . Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family. Immunogenetics. 2001; 53(4):279-87. DOI: 10.1007/s002510100325. View

14.

Mans J, Natarajan K, Balbo A, Schuck P, Eikel D, Hess S . Cellular expression and crystal structure of the murine cytomegalovirus major histocompatibility complex class I-like glycoprotein, m153. J Biol Chem. 2007; 282(48):35247-58. PMC: 2424207. DOI: 10.1074/jbc.M706782200. View

15.

Brunger A . Version 1.2 of the Crystallography and NMR system. Nat Protoc. 2007; 2(11):2728-33. DOI: 10.1038/nprot.2007.406. View

16.

Eagle R, Traherne J, Ashiru O, Wills M, Trowsdale J . Regulation of NKG2D ligand gene expression. Hum Immunol. 2006; 67(3):159-69. DOI: 10.1016/j.humimm.2006.02.015. View

17.

Gewurz B, Gaudet R, Tortorella D, Wang E, Ploegh H, Wiley D . Antigen presentation subverted: Structure of the human cytomegalovirus protein US2 bound to the class I molecule HLA-A2. Proc Natl Acad Sci U S A. 2001; 98(12):6794-9. PMC: 34432. DOI: 10.1073/pnas.121172898. View

18.

Wang R, Natarajan K, Margulies D . Structural basis of the CD8 alpha beta/MHC class I interaction: focused recognition orients CD8 beta to a T cell proximal position. J Immunol. 2009; 183(4):2554-64. PMC: 2782705. DOI: 10.4049/jimmunol.0901276. View

19.

Arapovic J, Lenac Rovis T, Reddy A, Krmpotic A, Jonjic S . Promiscuity of MCMV immunoevasin of NKG2D: m138/fcr-1 down-modulates RAE-1epsilon in addition to MULT-1 and H60. Mol Immunol. 2009; 47(1):114-22. DOI: 10.1016/j.molimm.2009.02.010. View

20.

Sissons J, Carmichael A, McKinney N, Sinclair J, Wills M . Human cytomegalovirus and immunopathology. Springer Semin Immunopathol. 2002; 24(2):169-85. DOI: 10.1007/s00281-002-0104-0. View