7y0h

Cryo-EM structure of human IgM-Fc in complex with the J chain and the P. falciparum VAR2CSA FCR3

spinqualitylabelsall models 7y0h, resolution 3.56Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7y0h is a 12 chain structure with sequence from Homo sapiens and Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.56Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. Plasmodium falciparum has evolved multiple mechanisms to hijack human immunoglobulin M.,Ji C, Shen H, Su C, Li Y, Chen S, Sharp TH, Xiao J Nat Commun. 2023 May 8;14(1):2650. doi: 10.1038/s41467-023-38320-z. PMID:37156765 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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