7UNY
Crystal structure of D2 nanobody in complex with PfCSS
Summary for 7UNY
| Entry DOI | 10.2210/pdb7uny/pdb |
| Descriptor | Cysteine-rich small secreted protein CSS, D2 Nanobody, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | 6-cys protein, nanobody, cell invasion |
| Biological source | Plasmodium falciparum (malaria parasite P. falciparum) More |
| Total number of polymer chains | 4 |
| Total formula weight | 99824.54 |
| Authors | Scally, S.W.,Lim, P.S.,Cowman, A.F. (deposition date: 2022-04-12, release date: 2022-11-23, Last modification date: 2024-10-23) |
| Primary citation | Scally, S.W.,Triglia, T.,Evelyn, C.,Seager, B.A.,Pasternak, M.,Lim, P.S.,Healer, J.,Geoghegan, N.D.,Adair, A.,Tham, W.H.,Dagley, L.F.,Rogers, K.L.,Cowman, A.F. PCRCR complex is essential for invasion of human erythrocytes by Plasmodium falciparum. Nat Microbiol, 7:2039-2053, 2022 Cited by PubMed Abstract: 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. PubMed: 36396942DOI: 10.1038/s41564-022-01261-2 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (4.13 Å) |
Structure validation
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