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New page: left|200px<br /><applet load="2flg" size="450" color="white" frame="true" align="right" spinBox="true" caption="2flg" /> '''Solution structure of an EGF-LIKE domain fro...
 
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[[Image:2flg.gif|left|200px]]<br /><applet load="2flg" size="450" color="white" frame="true" align="right" spinBox="true"
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'''Solution structure of an EGF-LIKE domain from the Plasmodium falciparum merozoite surface protein 1'''<br />


==Overview==
==Solution structure of an EGF-LIKE domain from the Plasmodium falciparum merozoite surface protein 1==
The Plasmodium falciparum merozoite surface protein-1 19 kDa fragment, (MSP-1(19)) comprises two closely packed EGF-like domains (EGF=epidermal, growth factor), each stabilized by three disulfide bonds. The native, conformation of this protein is important for eliciting P. falciparum, growth inhibitory antibodies. Here we show that the N-terminal EGF domain, alone can be chemically synthesized and efficiently refolded to a, native-like state, as shown by its solution structure as determined by NMR, spectroscopy. In order to study its immunogenicity, the domain was coupled, through its N terminus to a phospholipid and incorporated into, reconstituted influenza virus-like particles (virosomes). When used to, immunize mice, the peptide-loaded virosomes elicited potent humoral immune, responses that were shown by Western blots and immunofluorescence assays, to cross-react with native MSP-1 on the surfaces of P. falciparum blood, stage parasites. This opens the way for a medicinal chemistry-oriented, approach to the study and optimization of the antigenicity of the protein, as a potential malaria vaccine candidate, whilst exploiting the, immunopotentiating properties of influenza virosomes as a delivery, vehicle.
<StructureSection load='2flg' size='340' side='right'caption='[[2flg]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2flg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_isolate_WELLCOME Plasmodium falciparum isolate WELLCOME]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FLG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FLG FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=2flg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2flg OCA], [https://pdbe.org/2flg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2flg RCSB], [https://www.ebi.ac.uk/pdbsum/2flg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2flg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MSP1_PLAFW MSP1_PLAFW]
== 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/fl/2flg_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2flg ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Plasmodium falciparum merozoite surface protein-1 19 kDa fragment (MSP-1(19)) comprises two closely packed EGF-like domains (EGF=epidermal growth factor), each stabilized by three disulfide bonds. The native conformation of this protein is important for eliciting P. falciparum growth inhibitory antibodies. Here we show that the N-terminal EGF domain alone can be chemically synthesized and efficiently refolded to a native-like state, as shown by its solution structure as determined by NMR spectroscopy. In order to study its immunogenicity, the domain was coupled through its N terminus to a phospholipid and incorporated into reconstituted influenza virus-like particles (virosomes). When used to immunize mice, the peptide-loaded virosomes elicited potent humoral immune responses that were shown by Western blots and immunofluorescence assays to cross-react with native MSP-1 on the surfaces of P. falciparum blood stage parasites. This opens the way for a medicinal chemistry-oriented approach to the study and optimization of the antigenicity of the protein as a potential malaria vaccine candidate, whilst exploiting the immunopotentiating properties of influenza virosomes as a delivery vehicle.


==About this Structure==
Synthesis, solution structure and immune recognition of an epidermal growth factor-like domain from Plasmodium falciparum merozoite surface protein-1.,James S, Moehle K, Renard A, Mueller MS, Vogel D, Zurbriggen R, Pluschke G, Robinson JA Chembiochem. 2006 Dec;7(12):1943-50. PMID:17068840<ref>PMID:17068840</ref>
2FLG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FLG OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Synthesis, solution structure and immune recognition of an epidermal growth factor-like domain from Plasmodium falciparum merozoite surface protein-1., James S, Moehle K, Renard A, Mueller MS, Vogel D, Zurbriggen R, Pluschke G, Robinson JA, Chembiochem. 2006 Dec;7(12):1943-50. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17068840 17068840]
</div>
[[Category: Single protein]]
<div class="pdbe-citations 2flg" style="background-color:#fffaf0;"></div>
[[Category: James, S.]]
== References ==
[[Category: Moehle, K.]]
<references/>
[[Category: Pluschke, G.]]
__TOC__
[[Category: Robinson, J.]]
</StructureSection>
[[Category: NH2]]
[[Category: Large Structures]]
[[Category: egf-like domain]]
[[Category: Plasmodium falciparum isolate WELLCOME]]
[[Category: extracellular]]
[[Category: James S]]
[[Category: malaria vaccine component]]
[[Category: Moehle K]]
[[Category: modular protein]]
[[Category: Pluschke G]]
[[Category: surface antigen]]
[[Category: Robinson J]]
[[Category: surface protein]]
 
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