5mgt

Complex of human NKR-P1 and LLT1 in deglycosylated forms

spinqualitylabelsall models 5mgt, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5mgt is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: CL, NAG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CLC2D_HUMAN Receptor for KLRB1 that protects target cells against natural killer cell-mediated lysis. Inhibits osteoclast formation. Inhibits bone resorption. Modulates the release of interferon-gamma. Binds high molecular weight sulfated glycosaminoglycans. Publication Abstract from PubMed Signaling by the human C-type lectin-like receptor, natural killer (NK) cell inhibitory receptor NKR-P1, has a critical role in many immune-related diseases and cancer. C-type lectin-like receptors have weak affinities to their ligands; therefore, setting up a comprehensive model of NKR-P1-LLT1 interactions that considers the natural state of the receptor on the cell surface is necessary to understand its functions. Here we report the crystal structures of the NKR-P1 and NKR-P1:LLT1 complexes, which provides evidence that NKR-P1 forms homodimers in an unexpected arrangement to enable LLT1 binding in two modes, bridging two LLT1 molecules. These interaction clusters are suggestive of an inhibitory immune synapse. By observing the formation of these clusters in solution using SEC-SAXS analysis, by dSTORM super-resolution microscopy on the cell surface, and by following their role in receptor signaling with freshly isolated NK cells, we show that only the ligation of both LLT1 binding interfaces leads to effective NKR-P1 inhibitory signaling. In summary, our findings collectively support a model of NKR-P1:LLT1 clustering, which allows the interacting proteins to overcome weak ligand-receptor affinity and to trigger signal transduction upon cellular contact in the immune synapse. Structure of the human NK cell NKR-P1:LLT1 receptor:ligand complex reveals clustering in the immune synapse.,Blaha J, Skalova T, Kalouskova B, Skorepa O, Cmunt D, Grobarova V, Pazicky S, Polachova E, Abreu C, Stransky J, Koval T, Duskova J, Zhao Y, Harlos K, Hasek J, Dohnalek J, Vanek O Nat Commun. 2022 Aug 26;13(1):5022. doi: 10.1038/s41467-022-32577-6. PMID:36028489 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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