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Publication Abstract from PubMed

The NKG2D receptor is expressed on the surface of NK, T, and macrophage lineage cells and plays an important role in antiviral and antitumor immunity. To evade NKG2D recognition herpesviruses block the expression of NKG2D ligands on the surface of infected cells using a diverse repertoire of sabotage methods. Cow- and monkeypox viruses have taken an alternate approach by encoding a soluble NKG2D ligand, the orthopoxvirus MHC class I-like protein (OMCP), which can block NKG2D-mediated cytotoxicity. This approach has the advantage of targeting a single conserved receptor instead of numerous host ligands that exhibit significant sequence diversity. Herein we show that OMCP binds the NKG2D homodimer as a monomer and competitively blocks host ligand engagement. We have also determined the 2.25-A resolution crystal structure of OMCP from the cowpox virus Brighton Red strain, revealing a truncated MHC class I-like platform domain consisting of a beta sheet flanked with two anti-parallel alpha helices. OMCP is generally similar in structure to known host NKG2D ligands but has notable variations in regions typically used to engage NKG2D. Additionally, the determinants responsible for the 14-fold higher affinity of OMCP for human over murine NKG2D were mapped to a single loop in the NKG2D ligand-binding pocket.

Crystal structure of the cowpox virus encoded NKG2D-ligand OMCP.,Lazear E, Peterson LJ, Nelson CA, Fremont DH J Virol. 2012 Oct 31. PMID:23115291^[1]

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