7unz

Crystal structure of H2 nanobody in complex with PfCSS

spinqualitylabelsall models 7unz, resolution 2.03Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7unz is a 4 chain structure with sequence from Plasmodium falciparum and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.03Å Ligands: BMA, CSD, EDO, MLI, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The most severe form of malaria is caused by Plasmodium falciparum. These parasites invade human erythrocytes, and an essential step in this process involves the ligand PfRh5, which forms a complex with cysteine-rich protective antigen (CyRPA) and PfRh5-interacting protein (PfRipr) (RCR complex) and binds basigin on the host cell. We identified a heteromeric disulfide-linked complex consisting of P. falciparum Plasmodium thrombospondin-related apical merozoite protein (PfPTRAMP) and P. falciparum cysteine-rich small secreted protein (PfCSS) and have shown that it binds RCR to form a pentameric complex, PCRCR. Using P. falciparum lines with conditional knockouts, invasion inhibitory nanobodies to both PfPTRAMP and PfCSS, and lattice light-sheet microscopy, we show that they are essential for merozoite invasion. The PCRCR complex functions to anchor the contact between merozoite and erythrocyte membranes brought together by strong parasite deformations. We solved the structure of nanobody-PfCSS complexes to identify an inhibitory epitope. Our results define the function of the PCRCR complex and identify invasion neutralizing epitopes providing a roadmap for structure-guided development of these proteins for a blood stage malaria vaccine. PCRCR complex is essential for invasion of human erythrocytes by Plasmodium falciparum.,Scally SW, Triglia T, Evelyn C, Seager BA, Pasternak M, Lim PS, Healer J, Geoghegan ND, Adair A, Tham WH, Dagley LF, Rogers KL, Cowman AF Nat Microbiol. 2022 Dec;7(12):2039-2053. doi: 10.1038/s41564-022-01261-2. Epub , 2022 Nov 17. PMID:36396942 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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