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New page: left|200px<br /><applet load="1wa8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wa8" /> '''SOLUTION STRUCTURE OF THE CFP-10.ESAT-6 COMP...
 
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[[Image:1wa8.gif|left|200px]]<br /><applet load="1wa8" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1wa8" />
'''SOLUTION STRUCTURE OF THE CFP-10.ESAT-6 COMPLEX. MAJOR VIRULENCE DETERMINANTS OF PATHOGENIC MYCOBACTERIA'''<br />


==Overview==
==Solution Structure of the CFP-10.ESAT-6 Complex. Major Virulence Determinants of Pathogenic Mycobacteria==
The secreted Mycobacterium tuberculosis complex proteins CFP-10 and ESAT-6, have recently been shown to play an essential role in tuberculosis, pathogenesis. We have determined the solution structure of the tight, 1:1, complex formed by CFP-10 and ESAT-6, and employed fluorescence microscopy, to demonstrate specific binding of the complex to the surface of, macrophage and monocyte cells. A striking feature of the complex is the, long flexible arm formed by the C-terminus of CFP-10, which was found to, be essential for binding to the surface of cells. The surface features of, the CFP-10.ESAT-6 complex, together with observed binding to specific host, cells, strongly suggest a key signalling role for the complex, in which, binding to cell surface receptors leads to modulation of host cell, behaviour to the advantage of the pathogen.
<StructureSection load='1wa8' size='340' side='right'caption='[[1wa8]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1wa8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv] and [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_variant_bovis Mycobacterium tuberculosis variant bovis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WA8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WA8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1wa8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wa8 OCA], [https://pdbe.org/1wa8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wa8 RCSB], [https://www.ebi.ac.uk/pdbsum/1wa8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wa8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ESXB_MYCBO ESXB_MYCBO] A secreted protein. Acts as a strong host T-cell antigen. Involved in translocation of bacteria from the host (human) phagolysosome to the host cytoplasm. Might serve as a chaperone to prevent uncontrolled membrane lysis by its partner EsxA.[UniProtKB:P9WNK5]
== 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/wa/1wa8_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=1wa8 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The secreted Mycobacterium tuberculosis complex proteins CFP-10 and ESAT-6 have recently been shown to play an essential role in tuberculosis pathogenesis. We have determined the solution structure of the tight, 1:1 complex formed by CFP-10 and ESAT-6, and employed fluorescence microscopy to demonstrate specific binding of the complex to the surface of macrophage and monocyte cells. A striking feature of the complex is the long flexible arm formed by the C-terminus of CFP-10, which was found to be essential for binding to the surface of cells. The surface features of the CFP-10.ESAT-6 complex, together with observed binding to specific host cells, strongly suggest a key signalling role for the complex, in which binding to cell surface receptors leads to modulation of host cell behaviour to the advantage of the pathogen.


==About this Structure==
Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6.,Renshaw PS, Lightbody KL, Veverka V, Muskett FW, Kelly G, Frenkiel TA, Gordon SV, Hewinson RG, Burke B, Norman J, Williamson RA, Carr MD EMBO J. 2005 Jul 20;24(14):2491-8. Epub 2005 Jun 23. PMID:15973432<ref>PMID:15973432</ref>
1WA8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mycobacterium_bovis Mycobacterium bovis] and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1WA8 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6., Renshaw PS, Lightbody KL, Veverka V, Muskett FW, Kelly G, Frenkiel TA, Gordon SV, Hewinson RG, Burke B, Norman J, Williamson RA, Carr MD, EMBO J. 2005 Jul 20;24(14):2491-8. Epub 2005 Jun 23. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15973432 15973432]
</div>
[[Category: Mycobacterium bovis]]
<div class="pdbe-citations 1wa8" style="background-color:#fffaf0;"></div>
[[Category: Mycobacterium tuberculosis]]
== References ==
[[Category: Protein complex]]
<references/>
[[Category: Burke, B.]]
__TOC__
[[Category: Carr, M.D.]]
</StructureSection>
[[Category: Frenkiel, T.A.]]
[[Category: Large Structures]]
[[Category: Gordon, S.V.]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Hewinson, R.G.]]
[[Category: Mycobacterium tuberculosis variant bovis]]
[[Category: Kelly, G.]]
[[Category: Burke B]]
[[Category: Lightbody, K.L.]]
[[Category: Carr MD]]
[[Category: Muskett, F.W.]]
[[Category: Frenkiel TA]]
[[Category: Norman, J.]]
[[Category: Gordon SV]]
[[Category: Renshaw, P.S.]]
[[Category: Hewinson RG]]
[[Category: TBSGC, TB.Structural.Genomics.Consortium.]]
[[Category: Kelly G]]
[[Category: Veverka, V.]]
[[Category: Lightbody KL]]
[[Category: Williamson, R.A.]]
[[Category: Muskett FW]]
[[Category: cfp-10]]
[[Category: Norman J]]
[[Category: esat-6]]
[[Category: Renshaw PS]]
[[Category: four helix bundle]]
[[Category: Veverka V]]
[[Category: helix-turn-helix]]
[[Category: Williamson RA]]
[[Category: mycobacteria]]
[[Category: nmr]]
[[Category: pathogenesis]]
[[Category: protein structure initiative]]
[[Category: psi]]
[[Category: solution structure]]
[[Category: tb structural genomics consortium]]
[[Category: tbsgc]]
[[Category: tuberculosis]]
 
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