7y0h

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Current revision (06:31, 3 July 2025) (edit) (undo)
 
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7y0h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y0h OCA], [https://pdbe.org/7y0h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y0h RCSB], [https://www.ebi.ac.uk/pdbsum/7y0h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y0h ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7y0h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y0h OCA], [https://pdbe.org/7y0h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y0h RCSB], [https://www.ebi.ac.uk/pdbsum/7y0h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y0h ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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<div style="background-color:#fffaf0;">
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[https://www.uniprot.org/uniprot/IGHM_HUMAN IGHM_HUMAN] Autosomal agammaglobulinemia. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:8890099</ref>
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== Publication Abstract from PubMed ==
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== Function ==
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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.
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[https://www.uniprot.org/uniprot/IGHM_HUMAN IGHM_HUMAN] IgM antibodies play an important role in primary defense mechanisms. They have been shown to be involved in early recognition of external invaders like bacteria and viruses, cellular waste and modified self, as well as in recognition and elimination of precancerous and cancerous lesions. The membrane-bound form is found in the majority of normal B-cells alongside with IgD. Membrane-bound IgM induces the phosphorylation of CD79A and CD79B by the Src family of protein tyrosine kinases. It may cause death of cells by apoptosis. It is also found in soluble form, which represents about 30% of the total serum immunoglobulins where it is found almost exclusively as a homopentamer. After the antigen binds to the B-cell receptor, the secreted form is secreted in large amounts.<ref>PMID:3137579</ref>
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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<ref>PMID:37156765</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7y0h" style="background-color:#fffaf0;"></div>
== References ==
== References ==
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Current revision

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

PDB ID 7y0h

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