7p93 | pdb_00007p93

Crystal Structure of leukotoxin LukE from Staphylococcus aureus in complex with a sulfated ACKR1 N-terminal peptide

spinqualitylabelsall models 7p93, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7p93 is a 3 chain structure with sequence from Homo sapiens and Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.55Å Ligands: ACE, TYS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LUKEV_STAA8 Part of a bi-component leucotoxin that acts by forming pores in the membrane of the target cells. The activity of LukEv-LukDv to rabbit leukocytes is similar to that of the Panton-Valentine leucocidin (PVL). LukEv-LukDv is hemolytic to rabbit red blood cells although the activity is only 8% of gamma-hemolysin. Publication Abstract from PubMed Staphylococcus aureus (SA) leukocidin LukED belongs to a family of bicomponent pore forming toxins that play important roles in SA immune evasion and nutrient acquisition. LukED targets specific G protein-coupled chemokine receptors to lyse human erythrocytes (red blood cells) and leukocytes (white blood cells). The first recognition step of receptors is critical for specific cell targeting and lysis. The structural and molecular bases for this mechanism are not well understood but could constitute essential information to guide antibiotic development. Here, we characterized the interaction of LukE with chemokine receptors ACKR1, CCR2 and CCR5 using a combination of structural, pharmacological and computational approaches. First, crystal structures of LukE in complex with a small molecule mimicking sulfotyrosine side chain (p-cresyl sulfate) and with peptides containing sulfotyrosines issued from receptor sequences revealed the location of receptor sulfotyrosine binding sites in the toxins. Then, by combining previous and novel experimental data with protein docking, classical and accelerated weight histogram (AWH) molecular dynamics we propose models of the ACKR1-LukE and CCR5-LukE complexes. This work provides novel insights into chemokine receptor recognition by leukotoxins and suggests that the conserved sulfotyrosine binding pocket could be a target of choice for future drug development. Structural insights into recognition of chemokine receptors by Staphylococcus aureus leukotoxins.,Lambey P, Otun O, Cong X, Hoh F, Brunel L, Verdie P, Grison CM, Peysson F, Jeannot S, Durroux T, Bechara C, Granier S, Leyrat C Elife. 2022 Mar 21;11. pii: 72555. doi: 10.7554/eLife.72555. PMID:35311641 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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