6X87

CryoEM structure of the Plasmodium berghei circumsporozoite protein in complex with inhibitory mouse antibody 3D11.

6X87 の概要

• エントリーDOI: 10.2210/pdb6x87/pdb
• 関連するPDBエントリー: 6X8P 6X8Q 6X8S 6X8U
• EMDBエントリー: 22089
• 分子名称: 3D11 Fab heavy chain, 3D11 Fab kappa chain, Circumsporozoite protein (3 entities in total)
• 機能のキーワード: antibody, malaria, immune system
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 15
• 化学式量合計: 365547.47

構造登録者

Kucharska, I.,Thai, E.,Rubinstein, J.,Julien, J.P. (登録日: 2020-06-01, 公開日: 2020-12-02, 最終更新日: 2024-11-13)

主引用文献

Kucharska, I.,Thai, E.,Srivastava, A.,Rubinstein, J.L.,Pomes, R.,Julien, J.P.
Structural ordering of the Plasmodium berghei circumsporozoite protein repeats by inhibitory antibody 3D11.
Elife, 9:-, 2020

PubMed Abstract: Plasmodium sporozoites express circumsporozoite protein (CSP) on their surface, an essential protein that contains central repeating motifs. Antibodies targeting this region can neutralize infection, and the partial efficacy of RTS,S/AS01 - the leading malaria vaccine against (Pf) - has been associated with the humoral response against the repeats. Although structural details of antibody recognition of PfCSP have recently emerged, the molecular basis of antibody-mediated inhibition of other Plasmodium species via CSP binding remains unclear. Here, we analyze the structure and molecular interactions of potent monoclonal antibody (mAb) 3D11 binding to CSP (PbCSP) using molecular dynamics simulations, X-ray crystallography, and cryoEM. We reveal that mAb 3D11 can accommodate all subtle variances of the PbCSP repeating motifs, and, upon binding, induces structural ordering of PbCSP through homotypic interactions. Together, our findings uncover common mechanisms of antibody evolution in mammals against the CSP repeats of Plasmodium sporozoites.

PubMed: 33253113
DOI: 10.7554/eLife.59018

実験手法

ELECTRON MICROSCOPY (3.2 Å)