7UVH

Pfs230 domain 1 bound by RUPA-32 Fab

7UVH の概要

• エントリーDOI: 10.2210/pdb7uvh/pdb
• 分子名称: RUPA-32 Fab Heavy Chain, RUPA-32 Fab Light Chain, Gametocyte surface protein P230, ... (8 entities in total)
• 機能のキーワード: antibody-fragment, malaria transmission, cell invasion, cell invasion-immune system complex, cell invasion/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 140816.32

構造登録者

Ivanochko, D.,Newton, J.,Julien, J.P. (登録日: 2022-05-02, 公開日: 2023-02-15, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.59 Å)