View source for 7ytc


==Cryo-EM structure of human FcmR bound to IgM-Fc/J==
<StructureSection load='7ytc' size='340' side='right'caption='[[7ytc]], [[Resolution|resolution]] 3.39&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ytc]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YTC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YTC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.39&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=7ytc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ytc OCA], [https://pdbe.org/7ytc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ytc RCSB], [https://www.ebi.ac.uk/pdbsum/7ytc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ytc ProSAT]</span></td></tr>
</table>
== Disease ==
[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> 
== Function ==
[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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== Publication Abstract from PubMed ==
Immunoglobulin M (IgM) is the first antibody to emerge during embryonic development and the humoral immune response(1). IgM can exist in several distinct forms, including monomeric, membrane-bound IgM within the B cell receptor (BCR) complex, pentameric and hexameric IgM in serum and secretory IgM on the mucosal surface. FcmuR, the only IgM-specific receptor in mammals, recognizes different forms of IgM to regulate diverse immune responses(2-5). However, the underlying molecular mechanisms remain unknown. Here we delineate the structural basis of the FcmuR-IgM interaction by crystallography and cryo-electron microscopy. We show that two FcmuR molecules interact with a Fcmu-Cmu4 dimer, suggesting that FcmuR can bind to membrane-bound IgM with a 2:1 stoichiometry. Further analyses reveal that FcmuR-binding sites are accessible in the context of IgM BCR. By contrast, pentameric IgM can recruit four FcmuR molecules to bind on the same side and thereby facilitate the formation of an FcmuR oligomer. One of these FcmuR molecules occupies the binding site of the secretory component. Nevertheless, four FcmuR molecules bind to the other side of secretory component-containing secretory IgM, consistent with the function of FcmuR in the retrotransport of secretory IgM. These results reveal intricate mechanisms of IgM perception by FcmuR.

Immunoglobulin M perception by FcmuR.,Li Y, Shen H, Zhang R, Ji C, Wang Y, Su C, Xiao J Nature. 2023 Mar;615(7954):907-912. doi: 10.1038/s41586-023-05835-w. Epub 2023 , Mar 22. PMID:36949194<ref>PMID:36949194</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ytc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Li Y]]
[[Category: Shen H]]
[[Category: Xiao J]]