|
|
| (3 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Crystal structure of a motavizumab epitope-scaffold bound to motavizumab Fab== | | ==Crystal structure of a motavizumab epitope-scaffold bound to motavizumab Fab== |
| - | <StructureSection load='3qwo' size='340' side='right' caption='[[3qwo]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='3qwo' size='340' side='right'caption='[[3qwo]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qwo]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QWO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QWO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qwo]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QWO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QWO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ixt|3ixt]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=3qwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qwo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qwo RCSB], [http://www.ebi.ac.uk/pdbsum/3qwo PDBsum]</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=3qwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qwo OCA], [https://pdbe.org/3qwo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qwo RCSB], [https://www.ebi.ac.uk/pdbsum/3qwo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qwo ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| Line 15: |
Line 16: |
| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3qwo" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| | [[Category: Staphylococcus aureus]] | | [[Category: Staphylococcus aureus]] |
| - | [[Category: Kwong, P D]] | + | [[Category: Kwong PD]] |
| - | [[Category: McLellan, J S]] | + | [[Category: McLellan JS]] |
| - | [[Category: Immune complex]]
| + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
Publication Abstract from PubMed
Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, but an effective vaccine has not yet been developed. An ideal vaccine would elicit protective antibodies while avoiding virus-specific T-cell responses, which have been implicated in vaccine-enhanced disease with previous RSV vaccines. We propose that heterologous proteins designed to present RSV-neutralizing antibody epitopes and to elicit cognate antibodies have the potential to fulfill these vaccine requirements, as they can be fashioned to be free of viral T-cell epitopes. Here we present the design and characterization of three epitope-scaffolds that present the epitope of motavizumab, a potent neutralizing antibody that binds to a helix-loop-helix motif in the RSV fusion glycoprotein. Two of the epitope-scaffolds could be purified, and one epitope-scaffold based on a Staphylococcus aureus protein A domain bound motavizumab with kinetic and thermodynamic properties consistent with the free epitope-scaffold being stabilized in a conformation that closely resembled the motavizumab-bound state. This epitope-scaffold was well folded as assessed by circular dichroism and isothermal titration calorimetry, and its crystal structure (determined in complex with motavizumab to 1.9 A resolution) was similar to the computationally designed model, with all hydrogen-bond interactions critical for binding to motavizumab preserved. Immunization of mice with this epitope-scaffold failed to elicit neutralizing antibodies but did elicit sera with F binding activity. The elicitation of F binding antibodies suggests that some of the design criteria for eliciting protective antibodies without virus-specific T-cell responses are being met, but additional optimization of these novel immunogens is required.
Design and characterization of epitope-scaffold immunogens that present the motavizumab epitope from respiratory syncytial virus.,McLellan JS, Correia BE, Chen M, Yang Y, Graham BS, Schief WR, Kwong PD J Mol Biol. 2011 Jun 24;409(5):853-66. Epub 2011 Apr 27. PMID:21549714[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ McLellan JS, Correia BE, Chen M, Yang Y, Graham BS, Schief WR, Kwong PD. Design and characterization of epitope-scaffold immunogens that present the motavizumab epitope from respiratory syncytial virus. J Mol Biol. 2011 Jun 24;409(5):853-66. Epub 2011 Apr 27. PMID:21549714 doi:10.1016/j.jmb.2011.04.044
|
