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5tzn

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Structure of the viral immunoevasin m12 (Smith) bound to the natural killer cell receptor NKR-P1B (B6)

Structural highlights

5tzn is a 4 chain structure with sequence from Murid betaherpesvirus 1 and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KRBBB_MOUSE Receptor for CLEC2D/OCIL. Ligand-binding contributes to inhibition of cytotoxic natural killer (NK) cells. May mediate MHC class I-independent "missing-self" recognition of allografts, tumor cells and virus-infected cells.^[1] ^[2]

Publication Abstract from PubMed

Natural killer (NK) cells play a key role in innate immunity by detecting alterations in self and non-self ligands via paired NK cell receptors (NKRs). Despite identification of numerous NKR-ligand interactions, physiological ligands for the prototypical NK1.1 orphan receptor remain elusive. Here, we identify a viral ligand for the inhibitory and activating NKR-P1 (NK1.1) receptors. This murine cytomegalovirus (MCMV)-encoded protein, m12, restrains NK cell effector function by directly engaging the inhibitory NKR-P1B receptor. However, m12 also interacts with the activating NKR-P1A/C receptors to counterbalance m12 decoy function. Structural analyses reveal that m12 sequesters a large NKR-P1 surface area via a "polar claw" mechanism. Polymorphisms in, and ablation of, the viral m12 protein and host NKR-P1B/C alleles impact NK cell responses in vivo. Thus, we identify the long-sought foreign ligand for this key immunoregulatory NKR family and reveal how it controls the evolutionary balance of immune recognition during host-pathogen interplay.

A Viral Immunoevasin Controls Innate Immunity by Targeting the Prototypical Natural Killer Cell Receptor Family.,Aguilar OA, Berry R, Rahim MM, Reichel JJ, Popovic B, Tanaka M, Fu Z, Balaji GR, Lau TN, Tu MM, Kirkham CL, Mahmoud AB, Mesci A, Krmpotic A, Allan DS, Makrigiannis AP, Jonjic S, Rossjohn J, Carlyle JR Cell. 2017 Mar 23;169(1):58-71.e14. doi: 10.1016/j.cell.2017.03.002. PMID:28340350^[3]

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

References

↑ Iizuka K, Naidenko OV, Plougastel BF, Fremont DH, Yokoyama WM. Genetically linked C-type lectin-related ligands for the NKRP1 family of natural killer cell receptors. Nat Immunol. 2003 Aug;4(8):801-7. Epub 2003 Jul 13. PMID:12858173 doi:http://dx.doi.org/10.1038/ni954
↑ Carlyle JR, Jamieson AM, Gasser S, Clingan CS, Arase H, Raulet DH. Missing self-recognition of Ocil/Clr-b by inhibitory NKR-P1 natural killer cell receptors. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3527-32. Epub 2004 Feb 27. PMID:14990792 doi:http://dx.doi.org/10.1073/pnas.0308304101
↑ Aguilar OA, Berry R, Rahim MM, Reichel JJ, Popovic B, Tanaka M, Fu Z, Balaji GR, Lau TN, Tu MM, Kirkham CL, Mahmoud AB, Mesci A, Krmpotic A, Allan DS, Makrigiannis AP, Jonjic S, Rossjohn J, Carlyle JR. A Viral Immunoevasin Controls Innate Immunity by Targeting the Prototypical Natural Killer Cell Receptor Family. Cell. 2017 Mar 23;169(1):58-71.e14. doi: 10.1016/j.cell.2017.03.002. PMID:28340350 doi:http://dx.doi.org/10.1016/j.cell.2017.03.002