6MB3

Cryo-EM structure of the circumsporozoite protein of Plasmodium falciparum with a vaccine-elicited antibody reveals maturation of inter-antibody contacts

6MB3 の概要

• エントリーDOI: 10.2210/pdb6mb3/pdb
• EMDBエントリー: 9065
• 分子名称: Plasmodium falciparum recombinant shortened CSP, Fab311 heavy chain, Fab311 light chain (3 entities in total)
• 機能のキーワード: plasmodium falciparum, antibody, csp, rscsp, immune system
• 由来する生物種: Plasmodium falciparum; 詳細
• タンパク質・核酸の鎖数: 19
• 化学式量合計: 453946.41

構造登録者

Cottrell, C.A.,Torres, J.L.,Ward, A.B. (登録日: 2018-08-29, 公開日: 2018-10-31, 最終更新日: 2024-10-23)

主引用文献

Oyen, D.,Torres, J.L.,Cottrell, C.A.,Richter King, C.,Wilson, I.A.,Ward, A.B.
Cryo-EM structure ofP. falciparumcircumsporozoite protein with a vaccine-elicited antibody is stabilized by somatically mutated inter-Fab contacts.
Sci Adv, 4:eaau8529-eaau8529, 2018

PubMed Abstract: The circumsporozoite protein (CSP) on the surface of sporozoites is important for parasite development, motility, and host hepatocyte invasion. However, intrinsic disorder of the NANP repeat sequence in the central region of CSP has hindered its structural and functional characterization. Here, the cryo-electron microscopy structure at ~3.4-Å resolution of a recombinant shortened CSP construct with the variable domains (Fabs) of a highly protective monoclonal antibody reveals an extended spiral conformation of the central NANP repeat region surrounded by antibodies. This unusual structure appears to be stabilized and/or induced by interaction with an antibody where contacts between adjacent Fabs are somatically mutated and enhance the interaction. This maturation in non-antigen contact residues may be an effective mechanism for antibodies to target tandem repeat sequences and provide novel insights into malaria vaccine design.

PubMed: 30324137
DOI: 10.1126/sciadv.aau8529

実験手法

ELECTRON MICROSCOPY (3.37 Å)