7UVI

Pfs230 domain 1 bound by RUPA-55 Fab

Summary for 7UVI

• Entry DOI: 10.2210/pdb7uvi/pdb
• Related: 7UVH
• Descriptor: RUPA-55 Fab heavy chain, RUPA-55 Fab light chain, Gametocyte surface protein P230 (3 entities in total)
• Functional Keywords: antibody-fragment, malaria transmission, cell invasion, cell invasion-immune system complex, cell invasion/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 140381.49

Authors

Ivanochko, D.,Newton, J.,Julien, J.P. (deposition date: 2022-05-02, release date: 2023-02-15, Last modification date: 2024-10-30)

Primary citation

Ivanochko, D.,Fabra-Garcia, A.,Teelen, K.,van de Vegte-Bolmer, M.,van Gemert, G.J.,Newton, J.,Semesi, A.,de Bruijni, M.,Bolscher, J.,Ramjith, J.,Szabat, M.,Vogt, S.,Kraft, L.,Duncan, S.,Lee, S.M.,Kamya, M.R.,Feeney, M.E.,Jagannathan, P.,Greenhouse, B.,Sauerwein, R.W.,Richter King, C.,MacGill, R.S.,Bousema, T.,Jore, M.M.,Julien, J.P.
Potent transmission-blocking monoclonal antibodies from naturally exposed individuals target a conserved epitope on Plasmodium falciparum Pfs230.
Immunity, 56:420-432.e7, 2023

PubMed Abstract: Pfs230 is essential for Plasmodium falciparum transmission to mosquitoes and is the protein targeted by the most advanced malaria-transmission-blocking vaccine candidate. Prior understanding of functional epitopes on Pfs230 is based on two monoclonal antibodies (mAbs) with moderate transmission-reducing activity (TRA), elicited from subunit immunization. Here, we screened the B cell repertoire of two naturally exposed individuals possessing serum TRA and identified five potent mAbs from sixteen Pfs230 domain-1-specific mAbs. Structures of three potent and three low-activity antibodies bound to Pfs230 domain 1 revealed four distinct epitopes. Highly potent mAbs from natural infection recognized a common conformational epitope that is highly conserved across P. falciparum field isolates, while antibodies with negligible TRA derived from natural infection or immunization recognized three distinct sites. Our study provides molecular blueprints describing P. falciparum TRA, informed by contrasting potent and non-functional epitopes elicited by natural exposure and vaccination.

PubMed: 36792575
DOI: 10.1016/j.immuni.2023.01.013

Experimental method

X-RAY DIFFRACTION (2.92 Å)