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7jum

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Pfs230 D1 domain in complex with neutralizing antibody LMIV230-01

Structural highlights

7jum is a 6 chain structure with sequence from Homo sapiens 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 1.998Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

P230_PLAF7 Gametocyte surface protein required for male/female gamete fusion. Also required for male gamete exflagellation and interaction with erythrocytes.^[1]

Publication Abstract from PubMed

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.

A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes.,Coelho CH, Tang WK, Burkhardt M, Galson JD, Muratova O, Salinas ND, Alves E Silva TL, Reiter K, MacDonald NJ, Nguyen V, Herrera R, Shimp R, Narum DL, Byrne-Steele M, Pan W, Hou X, Brown B, Eisenhower M, Han J, Jenkins BJ, Doritchamou JYA, Smelkinson MG, Vega-Rodriguez J, Truck J, Taylor JJ, Sagara I, Healy SA, Renn JP, Tolia NH, Duffy PE Nat Commun. 2021 Mar 19;12(1):1750. doi: 10.1038/s41467-021-21955-1. PMID:33741942^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Eksi S, Czesny B, van Gemert GJ, Sauerwein RW, Eling W, Williamson KC. Malaria transmission-blocking antigen, Pfs230, mediates human red blood cell binding to exflagellating male parasites and oocyst production. Mol Microbiol. 2006 Aug;61(4):991-8. doi: 10.1111/j.1365-2958.2006.05284.x. PMID:16879650 doi:http://dx.doi.org/10.1111/j.1365-2958.2006.05284.x
↑ Coelho CH, Tang WK, Burkhardt M, Galson JD, Muratova O, Salinas ND, Alves E Silva TL, Reiter K, MacDonald NJ, Nguyen V, Herrera R, Shimp R, Narum DL, Byrne-Steele M, Pan W, Hou X, Brown B, Eisenhower M, Han J, Jenkins BJ, Doritchamou JYA, Smelkinson MG, Vega-Rodríguez J, Trück J, Taylor JJ, Sagara I, Healy SA, Renn JP, Tolia NH, Duffy PE. A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes. Nat Commun. 2021 Mar 19;12(1):1750. PMID:33741942 doi:10.1038/s41467-021-21955-1