| Structural highlights
6ohg is a 3 chain structure with sequence from Lk3 transgenic mice and Plafa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , |
| Gene: | PFS230, PF230, S230 (PLAFA) |
| 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
Proteins Pfs230 and Pfs48/45 are Plasmodium falciparum transmission-blocking (TB) vaccine candidates that form a membrane-bound protein complex on gametes. The biological role of Pfs230 or the Pfs230-Pfs48/45 complex remains poorly understood. Here, we present the crystal structure of recombinant Pfs230 domain 1 (Pfs230D1M), a 6-cysteine domain, in complex with the Fab fragment of a TB monoclonal antibody (mAb) 4F12. We observed the arrangement of Pfs230 on the surface of macrogametes differed from that on microgametes, and that Pfs230, with no known membrane anchor, may exist on the membrane surface in the absence of Pfs48/45. 4F12 appears to sterically interfere with Pfs230 function. Combining mAbs against different epitopes of Pfs230D1 or of Pfs230D1 and Pfs48/45, significantly increased TB activity. These studies elucidate a mechanism of action of the Pfs230D1 vaccine, model the functional activity induced by a polyclonal antibody response and support the development of TB vaccines targeting Pfs230D1 and Pfs230D1-Pfs48/45.
Structure and function of a malaria transmission blocking vaccine targeting Pfs230 and Pfs230-Pfs48/45 proteins.,Singh K, Burkhardt M, Nakuchima S, Herrera R, Muratova O, Gittis AG, Kelnhofer E, Reiter K, Smelkinson M, Veltri D, Swihart BJ, Shimp R Jr, Nguyen V, Zhang B, MacDonald NJ, Duffy PE, Garboczi DN, Narum DL Commun Biol. 2020 Jul 24;3(1):395. doi: 10.1038/s42003-020-01123-9. PMID:32709983[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
- ↑ Singh K, Burkhardt M, Nakuchima S, Herrera R, Muratova O, Gittis AG, Kelnhofer E, Reiter K, Smelkinson M, Veltri D, Swihart BJ, Shimp R Jr, Nguyen V, Zhang B, MacDonald NJ, Duffy PE, Garboczi DN, Narum DL. Structure and function of a malaria transmission blocking vaccine targeting Pfs230 and Pfs230-Pfs48/45 proteins. Commun Biol. 2020 Jul 24;3(1):395. doi: 10.1038/s42003-020-01123-9. PMID:32709983 doi:http://dx.doi.org/10.1038/s42003-020-01123-9
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