7ZWM

Pfs48/45 central and C-terminal domains bound to Fab fragments of monoclonal antibody 10D8 and 32F3

Summary for 7ZWM

• Entry DOI: 10.2210/pdb7zwm/pdb
• Descriptor: Gametocyte surface protein P45/48, 32F3 heavy chain, 32F3 light chain, ... (8 entities in total)
• Functional Keywords: pfs48/45, malaria, transmission-blocking, plasmodium falciparum, gamete, antibody, cell adhesion
• Biological source: Plasmodium falciparum (malaria parasite P. falciparum); More
• Total number of polymer chains: 10
• Total formula weight: 400980.05

Authors

Ko, K.T.,Lennartz, F.L.,Higgins, M.K. (deposition date: 2022-05-19, release date: 2022-06-22, Last modification date: 2024-01-31)

Primary citation

Ko, K.T.,Lennartz, F.,Mekhaiel, D.,Guloglu, B.,Marini, A.,Deuker, D.J.,Long, C.A.,Jore, M.M.,Miura, K.,Biswas, S.,Higgins, M.K.
Structure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies.
Nat Commun, 13:5603-5603, 2022

PubMed Abstract: An effective malaria vaccine remains a global health priority and vaccine immunogens which prevent transmission of the parasite will have important roles in multi-component vaccines. One of the most promising candidates for inclusion in a transmission-blocking malaria vaccine is the gamete surface protein Pfs48/45, which is essential for development of the parasite in the mosquito midgut. Indeed, antibodies which bind Pfs48/45 can prevent transmission if ingested with the parasite as part of the mosquito bloodmeal. Here we present the structure of full-length Pfs48/45, showing its three domains to form a dynamic, planar, triangular arrangement. We reveal where transmission-blocking and non-blocking antibodies bind on Pfs48/45. Finally, we demonstrate that antibodies which bind across this molecule can be transmission-blocking. These studies will guide the development of future Pfs48/45-based vaccine immunogens.

PubMed: 36153317
DOI: 10.1038/s41467-022-33379-6

Experimental method

X-RAY DIFFRACTION (3.69 Å)