6kxs

From Proteopedia

(Difference between revisions)

Revision as of 16:52, 15 December 2021

Cryo-EM structure of human IgM-Fc in complex with the J chain and the ectodomain of pIgR

6kxs, resolution 3.40Å

Structural highlights

6kxs is a 12 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	IGHM (HUMAN), JCHAIN, IGCJ, IGJ (HUMAN), PIGR (HUMAN)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[IGHM_HUMAN] Autosomal agammaglobulinemia. The disease is caused by mutations affecting the gene represented in this entry.^[1]

Function

[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.^[2] [PIGR_HUMAN] This receptor binds polymeric IgA and IgM at the basolateral surface of epithelial cells. The complex is then transported across the cell to be secreted at the apical surface. During this process a cleavage occurs that separates the extracellular (known as the secretory component) from the transmembrane segment. [IGJ_HUMAN] Serves to link two monomer units of either IgM or IgA. In the case of IgM, the J chain-joined dimer is a nucleating unit for the IgM pentamer, and in the case of IgA it induces larger polymers. It also help to bind these immunoglobulins to secretory component.[UniProtKB:P01592]

Publication Abstract from PubMed

Immunoglobulin M (IgM) plays a pivotal role in both humoral and mucosal immunity. Its assembly and transport depend on the joining chain (J-chain) and the polymeric immunoglobulin receptor (pIgR), but the underlying molecular mechanisms of these processes are unclear. We report a cryo-electron microscopy structure of the Fc region of human IgM in complex with the J-chain and pIgR ectodomain. The IgM-Fc pentamer is formed asymmetrically, resembling a hexagon with a missing triangle. The tailpieces of IgM-Fc pack into an amyloid-like structure to stabilize the pentamer. The J-chain caps the tailpiece assembly and bridges the interaction between IgM-Fc and the polymeric immunoglobulin receptor, which undergoes a large conformational change to engage the IgM-J complex. These results provide a structural basis for the function of IgM.

Structural insights into immunoglobulin M.,Li Y, Wang G, Li N, Wang Y, Zhu Q, Chu H, Wu W, Tan Y, Yu F, Su XD, Gao N, Xiao J Science. 2020 Feb 28;367(6481):1014-1017. doi: 10.1126/science.aaz5425. Epub 2020, Feb 6. PMID:32029689^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yel L, Minegishi Y, Coustan-Smith E, Buckley RH, Trubel H, Pachman LM, Kitchingman GR, Campana D, Rohrer J, Conley ME. Mutations in the mu heavy-chain gene in patients with agammaglobulinemia. N Engl J Med. 1996 Nov 14;335(20):1486-93. PMID:8890099 doi:http://dx.doi.org/10.1056/NEJM199611143352003
↑ Tisch R, Roifman CM, Hozumi N. Functional differences between immunoglobulins M and D expressed on the surface of an immature B-cell line. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6914-8. PMID:3137579
↑ Li Y, Wang G, Li N, Wang Y, Zhu Q, Chu H, Wu W, Tan Y, Yu F, Su XD, Gao N, Xiao J. Structural insights into immunoglobulin M. Science. 2020 Feb 28;367(6481):1014-1017. doi: 10.1126/science.aaz5425. Epub 2020, Feb 6. PMID:32029689 doi:http://dx.doi.org/10.1126/science.aaz5425

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6kxs"

@@ Line 3: / Line 3: @@
 <SX load='6kxs' size='340' side='right' viewer='molstar' caption='[[6kxs]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6kxs]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KXS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6KXS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6kxs]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KXS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KXS FirstGlance]. <br>
 </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'>[http://proteopedia.org/fgij/fg.htm?mol=6kxs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kxs OCA], [http://pdbe.org/6kxs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kxs RCSB], [http://www.ebi.ac.uk/pdbsum/6kxs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kxs ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGHM ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), JCHAIN, IGCJ, IGJ ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PIGR ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6kxs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kxs OCA], [https://pdbe.org/6kxs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kxs RCSB], [https://www.ebi.ac.uk/pdbsum/6kxs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kxs ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://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>
+[[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 ==
-[[http://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>  [[http://www.uniprot.org/uniprot/PIGR_HUMAN PIGR_HUMAN]] This receptor binds polymeric IgA and IgM at the basolateral surface of epithelial cells. The complex is then transported across the cell to be secreted at the apical surface. During this process a cleavage occurs that separates the extracellular (known as the secretory component) from the transmembrane segment. [[http://www.uniprot.org/uniprot/IGJ_HUMAN IGJ_HUMAN]] Serves to link two monomer units of either IgM or IgA. In the case of IgM, the J chain-joined dimer is a nucleating unit for the IgM pentamer, and in the case of IgA it induces larger polymers. It also help to bind these immunoglobulins to secretory component.[UniProtKB:P01592]
+[[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>  [[https://www.uniprot.org/uniprot/PIGR_HUMAN PIGR_HUMAN]] This receptor binds polymeric IgA and IgM at the basolateral surface of epithelial cells. The complex is then transported across the cell to be secreted at the apical surface. During this process a cleavage occurs that separates the extracellular (known as the secretory component) from the transmembrane segment. [[https://www.uniprot.org/uniprot/IGJ_HUMAN IGJ_HUMAN]] Serves to link two monomer units of either IgM or IgA. In the case of IgM, the J chain-joined dimer is a nucleating unit for the IgM pentamer, and in the case of IgA it induces larger polymers. It also help to bind these immunoglobulins to secretory component.[UniProtKB:P01592]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Immunoglobulin M (IgM) plays a pivotal role in both humoral and mucosal immunity. Its assembly and transport depend on the joining chain (J-chain) and the polymeric immunoglobulin receptor (pIgR), but the underlying molecular mechanisms of these processes are unclear. We report a cryo-electron microscopy structure of the Fc region of human IgM in complex with the J-chain and pIgR ectodomain. The IgM-Fc pentamer is formed asymmetrically, resembling a hexagon with a missing triangle. The tailpieces of IgM-Fc pack into an amyloid-like structure to stabilize the pentamer. The J-chain caps the tailpiece assembly and bridges the interaction between IgM-Fc and the polymeric immunoglobulin receptor, which undergoes a large conformational change to engage the IgM-J complex. These results provide a structural basis for the function of IgM.
+Structural insights into immunoglobulin M.,Li Y, Wang G, Li N, Wang Y, Zhu Q, Chu H, Wu W, Tan Y, Yu F, Su XD, Gao N, Xiao J Science. 2020 Feb 28;367(6481):1014-1017. doi: 10.1126/science.aaz5425. Epub 2020, Feb 6. PMID:32029689<ref>PMID:32029689</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6kxs" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </SX>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Li, Y]]

6kxs

From Proteopedia

Revision as of 16:52, 15 December 2021

Cryo-EM structure of human IgM-Fc in complex with the J chain and the ectodomain of pIgR

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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