2p9r

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[[Image:2p9r.jpg|left|200px]]
 
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==Human alpha2-macroglogulin is composed of multiple domains, as predicted by homology with complement component C3==
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The line below this paragraph, containing "STRUCTURE_2p9r", creates the "Structure Box" on the page.
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<StructureSection load='2p9r' size='340' side='right'caption='[[2p9r]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2p9r]] is a 2 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=2P9R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P9R FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</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=2p9r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p9r OCA], [https://pdbe.org/2p9r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p9r RCSB], [https://www.ebi.ac.uk/pdbsum/2p9r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p9r ProSAT]</span></td></tr>
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{{STRUCTURE_2p9r| PDB=2p9r | SCENE= }}
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</table>
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== Function ==
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'''Human alpha2-macroglogulin is composed of multiple domains, as predicted by homology with complement component C3'''
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[https://www.uniprot.org/uniprot/A2MG_HUMAN A2MG_HUMAN] Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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==Overview==
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Check<jmol>
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Human alpha2M (alpha2-macroglobulin) and the complement components C3 and C4 are thiol ester-containing proteins that evolved from the same ancestral gene. The recent structure determination of human C3 has allowed a detailed prediction of the location of domains within human alpha2M to be made. We describe here the expression and characterization of three alpha(2)M domains predicted to be involved in the stabilization of the thiol ester in native alpha2M and in its activation upon bait region proteolysis. The three newly expressed domains are MG2 (macroglobulin domain 2), TED (thiol ester-containing domain) and CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain. Together with the previously characterized RBD (receptor-binding domain), they represent approx. 42% of the alpha2M polypeptide. Their expression as folded domains strongly supports the predicted domain organization of alpha2M. An X-ray crystal structure of MG2 shows it to have a fibronectin type-3 fold analogous to MG1-MG8 of C3. TED is, as predicted, an alpha-helical domain. CUB is a spliced domain composed of two stretches of polypeptide that flank TED in the primary structure. In intact C3 TED interacts with RBD, where it is in direct contact with the thiol ester, and with MG2 and CUB on opposite, flanking sides. In contrast, these alpha2M domains, as isolated species, show negligible interaction with one another, suggesting that the native conformation of alpha2M, and the consequent thiol ester-stabilizing domain-domain interactions, result from additional restraints imposed by the physical linkage of these domains or by additional domains in the protein.
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p9/2p9r_consurf.spt"</scriptWhenChecked>
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==Disease==
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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Known disease associated with this structure: Emphysema due to alpha-2-macroglobulin deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=103950 103950]], Alzheimer disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=103950 103950]]
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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==About this Structure==
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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=2p9r ConSurf].
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2P9R is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P9R OCA].
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<div style="clear:both"></div>
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__TOC__
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==Reference==
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</StructureSection>
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Human alpha2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3., Doan N, Gettins PG, Biochem J. 2007 Oct 1;407(1):23-30. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17608619 17608619]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Doan, N.]]
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[[Category: Doan N]]
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[[Category: Human alpha2-macroglobulin]]
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[[Category: Mg2 domain]]
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[[Category: Signaling protein]]
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[[Category: X-ray]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 12:40:54 2008''
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Current revision

Human alpha2-macroglogulin is composed of multiple domains, as predicted by homology with complement component C3

PDB ID 2p9r

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