7uxl

Crystal structure of malaria transmission-blocking antigen Pfs48/45-6C variant in complex with human antibodies RUPA-44 and RUPA-29

spinqualitylabelsall models 7uxl, resolution 2.86Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7uxl is a 5 chain structure with sequence from Homo sapiens and Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.86Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Malaria transmission-blocking vaccines (TBVs) aim to induce antibodies that interrupt malaria parasite development in the mosquito, thereby blocking onward transmission, and provide a much-needed tool for malaria control and elimination. The parasite surface protein Pfs48/45 is a leading TBV candidate. Here, we isolated and characterized a panel of 81 human Pfs48/45-specific monoclonal antibodies (mAbs) from donors naturally exposed to Plasmodium parasites. Genetically diverse mAbs against each of the three domains (D1-D3) of Pfs48/45 were identified. The most potent mAbs targeted D1 and D3 and achieved >80% transmission-reducing activity in standard membrane-feeding assays, at 10 and 2 mug/mL, respectively. Co-crystal structures of D3 in complex with four different mAbs delineated two conserved protective epitopes. Altogether, these Pfs48/45-specific human mAbs provide important insight into protective and non-protective epitopes that can further our understanding of transmission and inform the design of refined malaria transmission-blocking vaccine candidates. Highly potent, naturally acquired human monoclonal antibodies against Pfs48/45 block Plasmodium falciparum transmission to mosquitoes.,Fabra-Garcia A, Hailemariam S, de Jong RM, Janssen K, Teelen K, van de Vegte-Bolmer M, van Gemert GJ, Ivanochko D, Semesi A, McLeod B, Vos MW, de Bruijni MHC, Bolscher JM, Szabat M, Vogt S, Kraft L, Duncan S, Kamya MR, Feeney ME, Jagannathan P, Greenhouse B, Dechering KJ, Sauerwein RW, King CR, MacGill RS, Bousema T, Julien JP, Jore MM Immunity. 2023 Feb 14;56(2):406-419.e7. doi: 10.1016/j.immuni.2023.01.009. PMID:36792574 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA