2q8b: Difference between revisions

New page: left|200px<br /> <applet load="2q8b" size="450" color="white" frame="true" align="right" spinBox="true" caption="2q8b, resolution 2.30Å" /> '''Structure of the ma...
 
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[[Image:2q8b.gif|left|200px]]<br />
<applet load="2q8b" size="450" color="white" frame="true" align="right" spinBox="true"
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'''Structure of the malaria antigen AMA1 in complex with a growth-inhibitory antibody'''<br />


==Overview==
==Structure of the malaria antigen AMA1 in complex with a growth-inhibitory antibody==
Identifying functionally critical regions of the malaria antigen AMA1, (apical membrane antigen 1) is necessary to understand the significance of, the polymorphisms within this antigen for vaccine development. The crystal, structure of AMA1 in complex with the Fab fragment of inhibitory, monoclonal antibody 1F9 reveals that 1F9 binds to the AMA1 solvent-exposed, hydrophobic trough, confirming its importance. 1F9 uses the heavy and, light chain complementarity-determining regions (CDRs) to wrap around the, polymorphic loops adjacent to the trough, but uses a ridge of framework, residues to bind to the hydrophobic trough. The resulting, 1F9-AMA1-combined buried surface of 2,470 A(2) is considerably larger than, previously reported Fab-antigen interfaces. Mutations of polymorphic AMA1, residues within the 1F9 epitope disrupt 1F9 binding and dramatically, reduce the binding of affinity-purified human antibodies. Moreover, 1F9, binding to AMA1 is competed by naturally acquired human antibodies, confirming that the 1F9 epitope is a frequent target of immunological, attack.
<StructureSection load='2q8b' size='340' side='right'caption='[[2q8b]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2q8b]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q8B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q8B FirstGlance]. <br>
</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=2q8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8b OCA], [https://pdbe.org/2q8b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q8b RCSB], [https://www.ebi.ac.uk/pdbsum/2q8b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q8b ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q7KQK5_PLAF7 Q7KQK5_PLAF7]
== 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/q8/2q8b_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=2q8b ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Identifying functionally critical regions of the malaria antigen AMA1 (apical membrane antigen 1) is necessary to understand the significance of the polymorphisms within this antigen for vaccine development. The crystal structure of AMA1 in complex with the Fab fragment of inhibitory monoclonal antibody 1F9 reveals that 1F9 binds to the AMA1 solvent-exposed hydrophobic trough, confirming its importance. 1F9 uses the heavy and light chain complementarity-determining regions (CDRs) to wrap around the polymorphic loops adjacent to the trough, but uses a ridge of framework residues to bind to the hydrophobic trough. The resulting 1F9-AMA1-combined buried surface of 2,470 A(2) is considerably larger than previously reported Fab-antigen interfaces. Mutations of polymorphic AMA1 residues within the 1F9 epitope disrupt 1F9 binding and dramatically reduce the binding of affinity-purified human antibodies. Moreover, 1F9 binding to AMA1 is competed by naturally acquired human antibodies, confirming that the 1F9 epitope is a frequent target of immunological attack.


==About this Structure==
Structure of the malaria antigen AMA1 in complex with a growth-inhibitory antibody.,Coley AM, Gupta A, Murphy VJ, Bai T, Kim H, Foley M, Anders RF, Batchelor AH PLoS Pathog. 2007 Sep 7;3(9):1308-19. PMID:17907804<ref>PMID:17907804</ref>
2Q8B is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2Q8B OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Structure of the malaria antigen AMA1 in complex with a growth-inhibitory antibody., Coley AM, Gupta A, Murphy VJ, Bai T, Kim H, Anders RF, Foley M, Batchelor AH, PLoS Pathog. 2007 Sep 7;3(9):1308-19. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17907804 17907804]
</div>
<div class="pdbe-citations 2q8b" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Plasmodium falciparum]]
[[Category: Plasmodium falciparum 3D7]]
[[Category: Single protein]]
[[Category: Anders RF]]
[[Category: Anders, R.F.]]
[[Category: Batchelor AH]]
[[Category: Batchelor, A.H.]]
[[Category: Gupta A]]
[[Category: Gupta, A.]]
[[Category: Murphy VJ]]
[[Category: Murphy, V.J.]]
[[Category: antigen-antibody complex]]
[[Category: immune system]]
 
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