View source for 5fob


==Crystal Structure of Human Complement C3b in complex with Smallpox Inhibitor of Complement (SPICE)==
<StructureSection load='5fob' size='340' side='right'caption='[[5fob]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5fob]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Variola_major_virus Variola major virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FOB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FOB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <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=5fob FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fob OCA], [https://pdbe.org/5fob PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fob RCSB], [https://www.ebi.ac.uk/pdbsum/5fob PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fob ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN] Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:[https://omim.org/entry/613779 613779]. A rare defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis.<ref>PMID:19913840</ref> <ref>PMID:9596584</ref> <ref>PMID:11387479</ref> <ref>PMID:15713468</ref> <ref>PMID:7961791</ref> [:]  Genetic variation in C3 is associated with susceptibility to age-related macular degeneration type 9 (ARMD9) [MIM:[https://omim.org/entry/611378 611378]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.<ref>PMID:19913840</ref> <ref>PMID:17634448</ref>   Defects in C3 are a cause of susceptibility to hemolytic uremic syndrome atypical type 5 (AHUS5) [MIM:[https://omim.org/entry/612925 612925]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.<ref>PMID:19913840</ref> <ref>PMID:18796626</ref> <ref>PMID:20513133</ref>   Note=Increased levels of C3 and its cleavage product ASP, are associated with obesity, diabetes and coronary heart disease. Short-term endurance training reduces baseline ASP levels and subsequently fat storage.<ref>PMID:19913840</ref> 
== Function ==
[https://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN] C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref>   Derived from proteolytic degradation of complement C3, C3a 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.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref>   Acylation stimulating protein (ASP): adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for GPR77. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of GPR77.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Regulators of complement activation (RCA) inhibit complement-induced immune responses on healthy host tissues. We present crystal structures of humanRCA(MCP, DAF, andCR1) and a smallpox virus homolog (SPICE) bound to complement component C3b. Our structural data reveal that up to four consecutive homologousCCPdomains (i-iv), responsible for inhibition, bind in the same orientation and extended arrangement at a shared binding platform on C3b. Large sequence variations inCCPdomains explain the diverse C3b-binding patterns, with limited or no contribution of some individual domains, while all regulators show extensive contacts with C3b for the domains at the third site. A variation of ~100 degrees rotation around the longitudinal axis is observed for domains binding at the fourth site on C3b, without affecting the overall binding mode. The data suggest a common evolutionary origin for both inhibitory mechanisms, called decay acceleration and cofactor activity, with variable C3b binding through domains at sites ii, iii, and iv, and provide a framework for understanding RCA disease-related mutations and immune evasion.

Regulators of complement activity mediate inhibitory mechanisms through a common C3b-binding mode.,Forneris F, Wu J, Xue X, Ricklin D, Lin Z, Sfyroera G, Tzekou A, Volokhina E, Granneman JC, Hauhart R, Bertram P, Liszewski MK, Atkinson JP, Lambris JD, Gros P EMBO J. 2016 Mar 24. pii: e201593673. PMID:27013439<ref>PMID:27013439</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5fob" style="background-color:#fffaf0;"></div>

==See Also==
*[[Complement C3 3D structures|Complement C3 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Variola major virus]]
[[Category: Forneris F]]
[[Category: Gros P]]
[[Category: Wu J]]
[[Category: Xue X]]