7JUM

Pfs230 D1 domain in complex with neutralizing antibody LMIV230-01

Summary for 7JUM

• Entry DOI: 10.2210/pdb7jum/pdb
• Descriptor: Gametocyte surface protein P230, Neutralizing antibody, LMIV230-01 Single-chain Fv (3 entities in total)
• Functional Keywords: pfs230d1, pfs230, monoclonal antibody, cell invasion
• Biological source: Plasmodium falciparum (isolate 3D7); More
• Total number of polymer chains: 6
• Total formula weight: 147108.20

Authors

Tolia, N.,Tang, W.K. (deposition date: 2020-08-20, release date: 2021-03-31, Last modification date: 2024-11-06)

Primary citation

Coelho, C.H.,Tang, W.K.,Burkhardt, M.,Galson, J.D.,Muratova, O.,Salinas, N.D.,Alves E Silva, T.L.,Reiter, K.,MacDonald, N.J.,Nguyen, V.,Herrera, R.,Shimp, R.,Narum, D.L.,Byrne-Steele, M.,Pan, W.,Hou, X.,Brown, B.,Eisenhower, M.,Han, J.,Jenkins, B.J.,Doritchamou, J.Y.A.,Smelkinson, M.G.,Vega-Rodriguez, J.,Truck, J.,Taylor, J.J.,Sagara, I.,Renn, J.P.,Tolia, N.H.,Duffy, P.E.
A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes.
Nat Commun, 12:1750-1750, 2021

PubMed Abstract: Malaria elimination requires tools that interrupt parasite transmission. Here, we characterize B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230 kDa gamete surface protein Pfs230, a key protein in sexual stage development of P. falciparum parasites. Among nine Pfs230 human monoclonal antibodies (mAbs) that we generated, one potently blocks transmission to mosquitoes in a complement-dependent manner and reacts to the gamete surface; the other eight show only low or no blocking activity. The structure of the transmission-blocking mAb in complex with vaccine antigen reveals a large discontinuous conformational epitope, specific to domain 1 of Pfs230 and comprising six structural elements in the protein. The epitope is conserved, suggesting the transmission-blocking mAb is broadly functional. This study provides a rational basis to improve malaria vaccines and develop therapeutic antibodies for malaria elimination.

PubMed: 33741942
DOI: 10.1038/s41467-021-21955-1

Experimental method

X-RAY DIFFRACTION (1.998 Å)