7U9W

Pfs230 D1 domain in complex with 230AS-88

Summary for 7U9W

• Entry DOI: 10.2210/pdb7u9w/pdb
• Descriptor: Gametocyte surface protein P230, 230AS-88 (3 entities in total)
• Functional Keywords: antibody, plasmodium falciparum, pfs230, transmission blocking, cell invasion
• Biological source: Plasmodium falciparum (malaria parasite P. falciparum); More
• Total number of polymer chains: 2
• Total formula weight: 48691.50

Authors

Tang, W.K.,Tolia, N.H. (deposition date: 2022-03-11, release date: 2023-02-15, Last modification date: 2023-10-25)

Primary citation

Tang, W.K.,Coelho, C.H.,Miura, K.,Nguemwo Tentokam, B.C.,Salinas, N.D.,Narum, D.L.,Healy, S.A.,Sagara, I.,Long, C.A.,Duffy, P.E.,Tolia, N.H.
A human antibody epitope map of Pfs230D1 derived from analysis of individuals vaccinated with a malaria transmission-blocking vaccine.
Immunity, 56:433-443.e5, 2023

PubMed Abstract: Pfs230 domain 1 (Pfs230D1) is an advanced malaria transmission-blocking vaccine antigen demonstrating high functional activity in clinical trials. However, the structural and functional correlates of transmission-blocking activity are not defined. Here, we characterized a panel of human monoclonal antibodies (hmAbs) elicited in vaccinees immunized with Pfs230D1. These hmAbs exhibited diverse transmission-reducing activity, yet all bound to Pfs230D1 with nanomolar affinity. We compiled epitope-binning data for seventeen hmAbs and structures of nine hmAbs complexes to construct a high-resolution epitope map and revealed that potent transmission-reducing hmAbs bound to one face of Pfs230D1, while non-potent hmAbs bound to the opposing side. The structure of Pfs230D1D2 revealed that non-potent transmission-reducing epitopes were occluded by the second domain. The hmAb epitope map delineated binary hmAb combinations that synergized for extremely high-potency, transmission-reducing activity. This work provides a high-resolution guide for structure-based design of enhanced immunogens and informs diagnostics that measure the transmission-reducing response.

PubMed: 36792576
DOI: 10.1016/j.immuni.2023.01.012

Experimental method

X-RAY DIFFRACTION (2.79 Å)