View source for 8adz


==Cryo-EM structure of full-length human immunoglobulin M - F(ab')2 conformation 2==
<StructureSection load='8adz' size='340' side='right'caption='[[8adz]], [[Resolution|resolution]] 6.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8adz]] is a 17 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=8ADZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ADZ 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]] 6.7&#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=8adz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8adz OCA], [https://pdbe.org/8adz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8adz RCSB], [https://www.ebi.ac.uk/pdbsum/8adz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8adz 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 ==
Immunoglobulin M (IgM) is the most ancient of the five isotypes of immunoglobulin (Ig) molecules and serves as the first line of defence against pathogens. Here, we use cryo-EM to image the structure of the human full-length IgM pentamer, revealing antigen binding domains flexibly attached to the asymmetric and rigid core formed by the Cmu4 and Cmu3 constant regions and the J-chain. A hinge is located at the Cmu3/Cmu2 domain interface, allowing Fabs and Cmu2 to pivot as a unit both in-plane and out-of-plane. This motion is different from that observed in IgG and IgA, where the two Fab arms are able to swing independently. A biased orientation of one pair of Fab arms results from asymmetry in the constant domain (Cmu3) at the IgM subunit interacting most extensively with the J-chain. This may influence the multi-valent binding to surface-associated antigens and complement pathway activation. By comparison, the structure of the Fc fragment in the IgM monomer is similar to that of the pentamer, but is more dynamic in the Cmu4 domain.

Cryomicroscopy reveals the structural basis for a flexible hinge motion in the immunoglobulin M pentamer.,Chen Q, Menon R, Calder LJ, Tolar P, Rosenthal PB Nat Commun. 2022 Oct 23;13(1):6314. doi: 10.1038/s41467-022-34090-2. PMID:36274064<ref>PMID:36274064</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8adz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chen Q]]
[[Category: Rosenthal P]]
[[Category: Tolar P]]