6OHG

Structure of Plasmodium falciparum vaccine candidate Pfs230D1M in complex with the Fab of a transmission blocking antibody

Summary for 6OHG

• Entry DOI: 10.2210/pdb6ohg/pdb
• Descriptor: Gametocyte surface protein P230, 4F12 Light Chain, 4F12 Heavy chain, ... (9 entities in total)
• Functional Keywords: malaria, transmission blocking, sexual stage, 6 cysteine-rich pfs230, immune system
• Biological source: Plasmodium falciparum; More
• Total number of polymer chains: 3
• Total formula weight: 71554.18

Authors

Garboczi, D.N.,Singh, K.,Gittis, A.G. (deposition date: 2019-04-05, release date: 2020-06-17, Last modification date: 2024-11-20)

Primary citation

Singh, K.,Burkhardt, M.,Nakuchima, S.,Herrera, R.,Muratova, O.,Gittis, A.G.,Kelnhofer, E.,Reiter, K.,Smelkinson, M.,Veltri, D.,Swihart, B.J.,Shimp Jr., R.,Nguyen, V.,Zhang, B.,MacDonald, N.J.,Duffy, P.E.,Garboczi, D.N.,Narum, D.L.
Structure and function of a malaria transmission blocking vaccine targeting Pfs230 and Pfs230-Pfs48/45 proteins.
Commun Biol, 3:395-395, 2020

PubMed Abstract: 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.

PubMed: 32709983
DOI: 10.1038/s42003-020-01123-9

Experimental method

X-RAY DIFFRACTION (2.385 Å)