4xt3

Structure of a viral GPCR bound to human chemokine CX3CL1

spinqualitylabelsall models 4xt3, resolution 3.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4xt3 is a 2 chain structure with sequence from Cytomegalovirus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.801Å Ligands: NAG, PCA, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function US28_HCMVA Receptor for a C-C type chemokine. Binds to a number of different CC-chemokines including CCL5/RANTES, CCL2/MCP-1, CCL3/MIP-1-alpha as well as CX3CL1/Fractalkine. Transduces signals resulting in the activation of MAP kinase signaling pathways and augmentation of intracellular calcium ion levels, leading to alterations in chemotactic behavior of vascular smooth muscle cells and macrophages. The US28 receptor also exhibits high levels of agonist-independent signaling activity and agonist-independent endocytosis. Interacts with endogenous Gaq/11 subunits and thereby constitutively activates phospholipase C. Publication Abstract from PubMed Chemokines are small proteins that function as immune modulators through activation of chemokine G protein-coupled receptors (GPCRs). Several viruses also encode chemokines and chemokine receptors to subvert the host immune response. How protein ligands activate GPCRs remains unknown. We report the crystal structure at 2.9 angstrom resolution of the human cytomegalovirus GPCR US28 in complex with the chemokine domain of human CX3CL1 (fractalkine). The globular body of CX3CL1 is perched on top of the US28 extracellular vestibule, whereas its amino terminus projects into the central core of US28. The transmembrane helices of US28 adopt an active-state-like conformation. Atomic-level simulations suggest that the agonist-independent activity of US28 may be due to an amino acid network evolved in the viral GPCR to destabilize the receptor's inactive state. Structural biology. Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor.,Burg JS, Ingram JR, Venkatakrishnan AJ, Jude KM, Dukkipati A, Feinberg EN, Angelini A, Waghray D, Dror RO, Ploegh HL, Garcia KC Science. 2015 Mar 6;347(6226):1113-7. doi: 10.1126/science.aaa5026. PMID:25745166 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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