5wb2

US28 bound to engineered chemokine CX3CL1.35 and nanobodies

spinqualitylabelsall models 5wb2, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5wb2 is a 3 chain structure with sequence from Hcmv, Human and Synthetic construct sequences. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CLR, MES, OLC, ZN NonStd Res: PCA, YCM Gene: US28 (HCMV), CX3CL1 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Human cytomegalovirus has hijacked and evolved a human G-protein-coupled receptor into US28, which functions as a promiscuous chemokine 'sink' to facilitate evasion of host immune responses. To probe the molecular basis of US28's unique ligand cross-reactivity, we deep-sequenced CX3CL1 chemokine libraries selected on 'molecular casts' of the US28 active-state and find that US28 can engage thousands of distinct chemokine sequences, many of which elicit diverse signaling outcomes. The structure of a G-protein-biased CX3CL1-variant in complex with US28 revealed an entirely unique chemokine amino terminal peptide conformation and remodeled constellation of receptor-ligand interactions. Receptor signaling, however, is remarkably robust to mutational disruption of these interactions. Thus, US28 accommodates and functionally discriminates amongst highly degenerate chemokine sequences by sensing the steric bulk of the ligands, which distort both receptor extracellular loops and the walls of the ligand binding pocket to varying degrees, rather than requiring sequence-specific bonding chemistries for recognition and signaling. Viral GPCR US28 can signal in response to chemokine agonists of nearly unlimited structural degeneracy.,Miles TF, Spiess K, Jude KM, Tsutsumi N, Burg JS, Ingram JR, Waghray D, Hjorto GM, Larsen O, Ploegh HL, Rosenkilde MM, Garcia KC Elife. 2018 Jun 8;7. pii: 35850. doi: 10.7554/eLife.35850. PMID:29882741 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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