8ukh

Crystal structure of Plasmodium falciparum CelTOS in complex with antibody 4h12

spinqualitylabelsall models 8ukh, resolution 3.52Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ukh is a 12 chain structure with sequence from Mus musculus and Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.52Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8I5P1_PLAF7 Publication Abstract from PubMed CelTOS is a malaria vaccine antigen that is conserved in Plasmodium and other apicomplexan parasites and plays a role in cell-traversal. The structural basis and mechanisms of CelTOS-induced protective immunity to parasites are unknown. Here, CelTOS-specific monoclonal antibodies (mAbs) 7g7 and 4h12 demonstrated multistage activity, protecting against liver infection and preventing parasite transmission to mosquitoes. Both mAbs demonstrated cross-species activity with sterile protection against in vivo challenge with transgenic parasites containing either P. falciparum or P. vivax CelTOS, and with transmission reducing activity against P. falciparum. The mAbs prevented CelTOS-mediated pore formation providing insight into the protective mechanisms. X-ray crystallography and mutant-library epitope mapping revealed two distinct broadly conserved neutralizing epitopes. 7g7 bound to a parallel dimer of CelTOS, while 4h12 bound to a novel antiparallel dimer architecture. These findings inform the design of antibody therapies and vaccines and raise the prospect of a single intervention to simultaneously combat P. falciparum and P. vivax malaria. Multistage protective anti-CelTOS monoclonal antibodies with cross-species sterile protection against malaria.,Tang WK, Salinas ND, Kolli SK, Xu S, Urusova DV, Kumar H, Jimah JR, Subramani PA, Ogbondah MM, Barnes SJ, Adams JH, Tolia NH Nat Commun. 2024 Aug 29;15(1):7487. doi: 10.1038/s41467-024-51701-2. PMID:39209843 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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