4FFE
The structure of cowpox virus CPXV018 (OMCP)
Summary for 4FFE
| Entry DOI | 10.2210/pdb4ffe/pdb |
| Related | 1HYR 1JE6 1JFM 1KCG 1PQZ 2VAB |
| Descriptor | CPXV018 protein (2 entities in total) |
| Functional Keywords | viral immune evasion proteins, structural genomics, nkg2d decoy ligand, niaid, national institute of allergy and infectious diseases, center for structural genomics of infectious diseases, csgid, secreted, nkg2d binding, fcrl5 binding, viral protein |
| Biological source | Cowpox virus (CPXV) |
| Total number of polymer chains | 3 |
| Total formula weight | 54195.67 |
| Authors | Lazear, E.,Peterson, L.W.,Nelson, C.A.,Fremont, D.H.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2012-06-01, release date: 2012-06-20, Last modification date: 2024-10-16) |
| Primary citation | Lazear, E.,Peterson, L.W.,Nelson, C.A.,Fremont, D.H. Crystal Structure of the Cowpox Virus-Encoded NKG2D Ligand OMCP. J.Virol., 87:840-850, 2013 Cited by PubMed Abstract: 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. Cowpox and monkeypox viruses have taken an alternate approach by encoding a soluble NKG2D ligand, the orthopoxvirus major histocompatibility complex (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. Here, we show that OMCP binds the NKG2D homodimer as a monomer and competitively blocks host ligand engagement. We have also determined the 2.25-Å-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 antiparallel 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 than for murine NKG2D were mapped to a single loop in the NKG2D ligand-binding pocket. PubMed: 23115291DOI: 10.1128/JVI.01948-12 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
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