7Y09

Cryo-EM structure of human IgM-Fc in complex with the J chain and the DBL domain of DBLMSP

Summary for 7Y09

• Entry DOI: 10.2210/pdb7y09/pdb
• EMDB information: 33538
• Descriptor: Putative erythrocyte membrane protein, Immunoglobulin heavy constant mu, Immunoglobulin J chain, ... (5 entities in total)
• Functional Keywords: malaria, immunoglobin, immune system
• Biological source: Plasmodium falciparum (malaria parasite P. falciparum); More
• Total number of polymer chains: 12
• Total formula weight: 511984.88

Authors

Shen, H.,Ji, C.,Xiao, J. (deposition date: 2022-06-03, release date: 2023-03-29, Last modification date: 2024-05-08)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.71 Å)