2p9r

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (09:08, 21 February 2024) (edit) (undo)
 
(14 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2p9r.jpg|left|200px]]<br /><applet load="2p9r" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="2p9r, resolution 2.3&Aring;" />
 
-
'''Human alpha2-macroglogulin is composed of multiple domains, as predicted by homology with complement component C3'''<br />
 
-
==Overview==
+
==Human alpha2-macroglogulin is composed of multiple domains, as predicted by homology with complement component C3==
-
Human alpha 2-macroglobulin (alpha 2-M) and the complement components C3, and C4 are thiolester-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 alpha 2-M 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 alpha 2-M, and in its activation upon bait region, proteolysis. The three newly-expressed domains are macroglobulin domain 2, (MG2), the thiolester-containing domain (TED) and the CUB domain. Together, with the previously characterized receptor binding domain (RBD) they, represent about 42% of the alpha 2-M polypeptide. Their expression as, folded domains strongly supports the predicted domain organization of, alpha 2-M. An x-ray crystal structure of MG2 shows it to have a, fibronectin 3-type fold analogous to MG domains 1-8 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 alpha 2-M domains, as isolated species, show negligible interaction, with one another, suggesting that the native conformation of alpha 2-M, 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.
+
<StructureSection load='2p9r' size='340' side='right'caption='[[2p9r]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
-
 
+
== Structural highlights ==
-
==About this Structure==
+
<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>
-
2P9R is a [http://en.wikipedia.org/wiki/Single_protein 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].
+
</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>
-
 
+
<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>
-
==Reference==
+
</table>
-
Human alpha 2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3., Doan N, Gettins PG, Biochem J. 2007 Jul 4;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17608619 17608619]
+
== Function ==
 +
[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.
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p9/2p9r_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</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].
 +
<div style="clear:both"></div>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Single protein]]
+
[[Category: Large Structures]]
-
[[Category: Doan, N.]]
+
[[Category: Doan N]]
-
[[Category: human alpha2-macroglobulin]]
+
-
[[Category: mg2 domain]]
+
-
[[Category: signaling protein]]
+
-
[[Category: x-ray]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:33:02 2008''
+

Current revision

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

PDB ID 2p9r

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2p9r"
Personal tools