7Y0J

Cryo-EM structure of human IgM-Fc in complex with the J chain and the P. falciparum TM284VAR1

7Y0J の概要

• エントリーDOI: 10.2210/pdb7y0j/pdb
• EMDBエントリー: 33547
• 分子名称: Erythrocyte membrane protein 2 variant TM284var1, Immunoglobulin heavy constant mu, Immunoglobulin J chain, ... (5 entities in total)
• 機能のキーワード: complex, antibody, immune system
• 由来する生物種: Plasmodium falciparum (malaria parasite P. falciparum); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 714382.69

構造登録者

Ji, C.,Xiao, J. (登録日: 2022-06-05, 公開日: 2023-04-05, 最終更新日: 2025-07-02)

主引用文献

Ji, C.,Shen, H.,Su, C.,Li, Y.,Chen, S.,Sharp, T.H.,Xiao, J.
Plasmodium falciparum has evolved multiple mechanisms to hijack human immunoglobulin M.
Nat Commun, 14:2650-2650, 2023

PubMed Abstract: Plasmodium falciparum causes the most severe malaria in humans. Immunoglobulin M (IgM) serves as the first line of humoral defense against infection and potently activates the complement pathway to facilitate P. falciparum clearance. A number of P. falciparum proteins bind IgM, leading to immune evasion and severe disease. However, the underlying molecular mechanisms remain unknown. Here, using high-resolution cryo-electron microscopy, we delineate how P. falciparum proteins VAR2CSA, TM284VAR1, DBLMSP, and DBLMSP2 target IgM. Each protein binds IgM in a different manner, and together they present a variety of Duffy-binding-like domain-IgM interaction modes. We further show that these proteins interfere directly with IgM-mediated complement activation in vitro, with VAR2CSA exhibiting the most potent inhibitory effect. These results underscore the importance of IgM for human adaptation of P. falciparum and provide critical insights into its immune evasion mechanism.

PubMed: 37156765
DOI: 10.1038/s41467-023-38320-z

実験手法

ELECTRON MICROSCOPY (3.62 Å)