9p6v: Difference between revisions
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The entry | ==Cryo-EM structure of chimeric immunoglobulin M comprising bony fish and human sequences, hFcm-tFcm-chi4== | ||
<StructureSection load='9p6v' size='340' side='right'caption='[[9p6v]], [[Resolution|resolution]] 3.92Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9p6v]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Oncorhynchus_mykiss Oncorhynchus mykiss]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9P6V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9P6V 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]] 3.92Å</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=9p6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9p6v OCA], [https://pdbe.org/9p6v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9p6v RCSB], [https://www.ebi.ac.uk/pdbsum/9p6v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9p6v 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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Polymeric (p) immunoglobulins (Igs) play critical roles in vertebrate immunity. IgM is the evolutionarily oldest pIg and functions both in circulation and in the mucosa. pIgM typically comprises between four and six IgM monomers and up to one joining chain (JC), which in mammals facilitates pIg assembly and promotes delivery to mucosal secretions. Bony fish (teleosts) lack JC and assemble tetrameric IgM whereas humans can express JC-containing pentamers and JC-free hexamers. Here we report cryo-electron microscopy structures of two JC-free chimeric IgM, comprising bony fish and human sequences, and the structure of human hexameric IgM. Chimeric IgM structures adopted unique pentameric geometry distinct from both human and fish pIgM whereas the human hexameric IgM structure adopted hexagonal geometry similar to JC-containing pentameric IgM, albeit with structural differences in center of the molecule. Together results provide new insights on how IgM heavy chain motifs contribute to JC-free pIgM assembly and reveal plasticity of this process, which can be manipulated to create pIg structures not observed in nature. Moreover, we found that antigen-targeting chimeric IgM could neutralize C. difficile toxin cytotoxicity, indicating potential to engineer uniquely structured pIgs to prevent or treat disease. | |||
Chimeric Immunoglobulin and human Immunoglobulin M structures provide insights on joining-chain independent assembly and function.,Lyu M, Stadtmueller BM bioRxiv [Preprint]. 2025 Jul 14:2025.07.09.663956. doi: , 10.1101/2025.07.09.663956. PMID:40791433<ref>PMID:40791433</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9p6v" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Oncorhynchus mykiss]] | |||
[[Category: Lyu M]] | |||
[[Category: Stadtmueller BM]] | |||