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| ==Structure of mammalian C3 with an intact thioester at 3A resolution==
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| <StructureSection load='2b39' size='340' side='right'caption='[[2b39]], [[Resolution|resolution]] 3.00Å' scene=''>
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| == Structural highlights ==
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| <table><tr><td colspan='2'>[[2b39]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B39 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B39 FirstGlance]. <br>
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| </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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1c3d|1c3d]]</div></td></tr>
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| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2b39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b39 OCA], [https://pdbe.org/2b39 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b39 RCSB], [https://www.ebi.ac.uk/pdbsum/2b39 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b39 ProSAT]</span></td></tr>
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| </table>
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| == Function ==
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| [[https://www.uniprot.org/uniprot/CO3_BOVIN CO3_BOVIN]] 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 (By similarity). 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 (By similarity). Acylation stimulating protein: 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-internalization and recycling of GPR77 (By similarity).
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| == Evolutionary Conservation ==
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| [[Image:Consurf_key_small.gif|200px|right]]
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| Check<jmol>
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| <jmolCheckbox>
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| <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b3/2b39_consurf.spt"</scriptWhenChecked>
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| <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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| <text>to colour the structure by Evolutionary Conservation</text>
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| </jmolCheckbox>
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| </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2b39 ConSurf].
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| <div style="clear:both"></div>
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The third component of complement (C3) is a 190 kDa glycoprotein essential for eliciting the complement response. The protein consists of two polypeptide chains (alpha and beta) held together with a single disulfide bridge. The beta-chain is composed of six MG domains, one of which is shared with the alpha-chain. The disulfide bridge connecting the chains is positioned in the shared MG domain. The alpha-chain consists of the anaphylatoxin domain, three MG domains, a CUB domain, an alpha(6)/alpha(6)-barrel domain and the C-terminal C345c domain. An internal thioester in the alpha-chain of C3 (present in C4 but not in C5) is cleaved during complement activation. This mediates covalent attachment of the activated C3b to immune complexes and invading microorganisms, thereby opsonizing the target. We present the structure of bovine C3 determined at 3 Angstroms resolution. The structure shows that the ester is buried deeply between the thioester domain and the properdin binding domain, in agreement with the human structure. This domain interface is broken upon activation, allowing nucleophile access. The structure of bovine C3 clearly demonstrates that the main chain around the thioester undergoes a helical transition upon activation. This rearrangement is proposed to be the basis for the high level of reactivity of the thioester group. A strictly conserved glutamate residue is suggested to function catalytically in thioester proteins. Structure-based design of inhibitors of C3 activation may target a conserved pocket between the alpha-chain and the beta-chain of C3, which appears essential for conformational changes in C3.
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| The structure of bovine complement component 3 reveals the basis for thioester function.,Fredslund F, Jenner L, Husted LB, Nyborg J, Andersen GR, Sottrup-Jensen L J Mol Biol. 2006 Aug 4;361(1):115-27. Epub 2006 Jun 21. PMID:16831446<ref>PMID:16831446</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 2b39" style="background-color:#fffaf0;"></div>
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| ==See Also==
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| *[[Complement C3 3D structures|Complement C3 3D structures]]
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| == References ==
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| <references/>
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| __TOC__
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| </StructureSection>
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| [[Category: Bos taurus]]
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| [[Category: Large Structures]]
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| [[Category: Andersen, G R]]
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| [[Category: Fredslund, F]]
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| [[Category: Husted, L B]]
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| [[Category: Jenner, L]]
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| [[Category: Nyborg, J]]
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| [[Category: Sottrup-Jensen, L]]
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| [[Category: Complement]]
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| [[Category: Immune defense]]
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| [[Category: Immune system]]
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| [[Category: Thioester]]
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