4xam: Difference between revisions

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#REDIRECT [[5jtw]] This PDB entry is obsolete and replaced by 5jtw
==Complement component C4b==
<StructureSection load='4xam' size='340' side='right'caption='[[4xam]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4xam]] is a 6 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=4XAM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XAM FirstGlance]. <br>
</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=4xam FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xam OCA], [https://pdbe.org/4xam PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xam RCSB], [https://www.ebi.ac.uk/pdbsum/4xam PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xam ProSAT]</span></td></tr>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/CO4A_HUMAN CO4A_HUMAN]] Defects in C4A are the cause of complement component 4A deficiency (C4AD) [MIM:[https://omim.org/entry/614380 614380]]. A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus with or without associated glomerulonephritis.<ref>PMID:8473511</ref>  Defects in C4A are a cause of susceptibility to systemic lupus erythematosus (SLE) [MIM:[https://omim.org/entry/152700 152700]]. A chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system. Note=Interindividual copy-number variation (CNV) of complement component C4 and associated polymorphisms result in different susceptibilities to SLE. The risk of SLE susceptibility has been shown to be significantly increased among subjects with only two copies of total C4. A high copy number is a protective factor against SLE.<ref>PMID:17503323</ref> 
== Function ==
[[https://www.uniprot.org/uniprot/CO4A_HUMAN CO4A_HUMAN]] C4 plays a central role in the activation of the classical pathway of the complement system. It is processed by activated C1 which removes from the alpha chain the C4a anaphylatoxin. The remaining alpha chain fragment C4b is the major activation product and is an essential subunit of the C3 convertase (C4b2a) and the C5 convertase (C3bC4b2a) enzymes of the classical complement pathway.  Derived from proteolytic degradation of complement C4, C4a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Complement component C4 is a central protein in the classical and lectin pathways within the complement system. During activation of complement, its major fragment C4b becomes covalently attached to the surface of pathogens and altered self-tissue, where it acts as an opsonin marking the surface for removal. Moreover, C4b provides a platform for assembly of the proteolytically active convertases that mediate downstream complement activation by cleavage of C3 and C5. In this article, we present the crystal and solution structures of the 195-kDa C4b. Our results provide the molecular details of the rearrangement accompanying C4 cleavage and suggest intramolecular flexibility of C4b. The conformations of C4b and its paralogue C3b are shown to be remarkably conserved, suggesting that the convertases from the classical and alternative pathways are likely to share their overall architecture and mode of substrate recognition. We propose an overall molecular model for the classical pathway C5 convertase in complex with C5, suggesting that C3b increases the affinity for the substrate by inducing conformational changes in C4b rather than a direct interaction with C5. C4b-specific features revealed by our structural studies are probably involved in the assembly of the classical pathway C3/C5 convertases and C4b binding to regulators.
 
Structural Basis for the Function of Complement Component C4 within the Classical and Lectin Pathways of Complement.,Mortensen S, Kidmose RT, Petersen SV, Szilagyi A, Prohaszka Z, Andersen GR J Immunol. 2015 Apr 24. pii: 1500087. PMID:25911760<ref>PMID:25911760</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4xam" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Complement C4|Complement C4]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Andersen, G R]]
[[Category: Kidmose, R T]]
[[Category: Mortensen, S]]
[[Category: Petersen, S V]]
[[Category: Szilagyi, A]]
[[Category: Alpha-2-macroglobulin family]]
[[Category: Complement component c4]]
[[Category: Immune system]]

Latest revision as of 12:46, 15 March 2023

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