6E63

Crystal structure of malaria transmission-blocking antigen Pfs48/45 6C in complex with antibody TB31F

6E63 の概要

• エントリーDOI: 10.2210/pdb6e63/pdb
• 分子名称: Pf48/45, TB31F Fab heavy chain, TB31F Fab light chain, ... (5 entities in total)
• 機能のキーワード: malaria, transmission-blocking, antigen, antibody, immune system
• 由来する生物種: Plasmodium falciparum; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 124871.01

構造登録者

Kundu, P.,Semesi, A.,Julien, J.P. (登録日: 2018-07-23, 公開日: 2018-11-28, 最終更新日: 2024-11-20)

主引用文献

Kundu, P.,Semesi, A.,Jore, M.M.,Morin, M.J.,Price, V.L.,Liang, A.,Li, J.,Miura, K.,Sauerwein, R.W.,King, C.R.,Julien, J.P.
Structural delineation of potent transmission-blocking epitope I on malaria antigen Pfs48/45.
Nat Commun, 9:4458-4458, 2018

PubMed Abstract: Interventions that can block the transmission of malaria-causing Plasmodium falciparum (Pf) between the human host and Anopheles vector have the potential to reduce the incidence of malaria. Pfs48/45 is a gametocyte surface protein critical for parasite development and transmission, and its targeting by monoclonal antibody (mAb) 85RF45.1 leads to the potent reduction of parasite transmission. Here, we reveal how the Pfs48/45 6C domain adopts a (SAG1)-related-sequence (SRS) fold. We structurally delineate potent epitope I and show how mAb 85RF45.1 recognizes an electronegative surface with nanomolar affinity. Analysis of Pfs48/45 sequences reveals that polymorphisms are rare for residues involved at the binding interface. Humanization of rat-derived mAb 85RF45.1 conserved the mode of recognition and activity of the parental antibody, while also improving its thermostability. Our work has implications for the development of transmission-blocking interventions, both through improving vaccine designs and the testing of passive delivery of mAbs in humans.

PubMed: 30367064
DOI: 10.1038/s41467-018-06742-9

実験手法

X-RAY DIFFRACTION (2.6 Å)