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| | ==Crystal structure of HIV epitope-scaffold 4E10_D0_1IS1A_001_C== | | ==Crystal structure of HIV epitope-scaffold 4E10_D0_1IS1A_001_C== |
| - | <StructureSection load='3lf9' size='340' side='right' caption='[[3lf9]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3lf9' size='340' side='right'caption='[[3lf9]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3lf9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LF9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LF9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3lf9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LF9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LF9 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3lf6|3lf6]], [[3lg7|3lg7]], [[3lh2|3lh2]], [[3lhp|3lhp]], [[3lef|3lef]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3lf9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lf9 OCA], [http://pdbe.org/3lf9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lf9 RCSB], [http://www.ebi.ac.uk/pdbsum/3lf9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lf9 ProSAT]</span></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=3lf9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lf9 OCA], [https://pdbe.org/3lf9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lf9 RCSB], [https://www.ebi.ac.uk/pdbsum/3lf9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lf9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
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| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lf/3lf9_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lf/3lf9_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Synthetic construct sequences]] | + | [[Category: Large Structures]] |
| - | [[Category: Holmes, M A]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Epitope-scaffold]] | + | [[Category: Holmes MA]] |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Broadly cross-reactive monoclonal antibodies define epitopes for vaccine development against HIV and other highly mutable viruses. Crystal structures are available for several such antibody-epitope complexes, but methods are needed to translate that structural information into immunogens that re-elicit similar antibodies. We describe a general computational method to design epitope-scaffolds in which contiguous structural epitopes are transplanted to scaffold proteins for conformational stabilization and immune presentation. Epitope-scaffolds designed for the poorly immunogenic but conserved HIV epitope 4E10 exhibited high epitope structural mimicry, bound with higher affinities to monoclonal antibody (mAb) 4E10 than the cognate peptide, and inhibited HIV neutralization by HIV+ sera. Rabbit immunization with an epitope-scaffold induced antibodies with structural specificity highly similar to mAb 4E10, an important advance toward elicitation of neutralizing activity. The results demonstrate that computationally designed epitope-scaffolds are valuable as structure-specific serological reagents and as immunogens to elicit antibodies with predetermined structural specificity.
Computational design of epitope-scaffolds allows induction of antibodies specific for a poorly immunogenic HIV vaccine epitope.,Correia BE, Ban YE, Holmes MA, Xu H, Ellingson K, Kraft Z, Carrico C, Boni E, Sather DN, Zenobia C, Burke KY, Bradley-Hewitt T, Bruhn-Johannsen JF, Kalyuzhniy O, Baker D, Strong RK, Stamatatos L, Schief WR Structure. 2010 Sep 8;18(9):1116-26. PMID:20826338[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Correia BE, Ban YE, Holmes MA, Xu H, Ellingson K, Kraft Z, Carrico C, Boni E, Sather DN, Zenobia C, Burke KY, Bradley-Hewitt T, Bruhn-Johannsen JF, Kalyuzhniy O, Baker D, Strong RK, Stamatatos L, Schief WR. Computational design of epitope-scaffolds allows induction of antibodies specific for a poorly immunogenic HIV vaccine epitope. Structure. 2010 Sep 8;18(9):1116-26. PMID:20826338 doi:10.1016/j.str.2010.06.010
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