6ntf: Difference between revisions
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==Crystal structure of a computationally optimized H5 influenza hemagglutinin== | |||
<StructureSection load='6ntf' size='340' side='right'caption='[[6ntf]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6ntf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Unidentified_influenza_virus Unidentified influenza virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NTF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NTF 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]] 2.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=6ntf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ntf OCA], [https://pdbe.org/6ntf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ntf RCSB], [https://www.ebi.ac.uk/pdbsum/6ntf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ntf ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Influenza A virus is a leading cause of death worldwide. Viruses of the H5 subtype have the potential to induce high mortality, and no vaccines are currently available to protect against H5 influenza viruses in the event of an outbreak. Experimental vaccination with one clade 2 virus does not protect against other subclades. The computationally optimized broadly reactive (COBRA) methodology was previously used to generate a H5 hemagglutinin (HA) antigen (COBRA2) that elicited increased serological breadth against multiple clade 2 H5N1 influenza viruses. In this report, we structurally and antigenically characterized the COBRA2 HA antigen. We examined the biochemical characteristics of the COBRA2 protein and determined the protein is correctly cleaved, properly folded into a trimeric structure, and antigenically correct by probing with HA head- and stem-specific monoclonal antibodies (mAbs). We further probed the antigenicity by examining binding of a panel of H5 mouse mAbs to the COBRA2 antigen, as well as several other HA antigens. We determined the X-ray crystal structure of the COBRA2 HA antigen to 2.8â¯A and the protein was observed to be in the expected trimeric form. The COBRA2 HA was structurally similar to the naturally occurring H5 HA antigens and suggests the protein folds similar to known HA structures. Overall, our data allow us to formulate a hypothesis on the mechanism of increased breadth due to vaccination with the COBRA2 HA antigen, which is that the protein incorporates antigenic sites from numerous HA antigens, and elicits mAbs with limited breadth, but with diversity in targeted antigenic sites. | |||
Structural and antigenic characterization of a computationally-optimized H5 hemagglutinin influenza vaccine.,Bar-Peled Y, Huang J, Nunez IA, Pierce SR, Ecker JW, Ross TM, Mousa JJ Vaccine. 2019 Sep 24;37(41):6022-6029. doi: 10.1016/j.vaccine.2019.08.062. Epub , 2019 Aug 31. PMID:31481254<ref>PMID:31481254</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Bar-Peled | <div class="pdbe-citations 6ntf" style="background-color:#fffaf0;"></div> | ||
[[Category: Huang | |||
[[Category: Mousa | ==See Also== | ||
*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Unidentified influenza virus]] | |||
[[Category: Bar-Peled Y]] | |||
[[Category: Huang J]] | |||
[[Category: Mousa JJ]] | |||
Latest revision as of 09:59, 11 October 2023
Crystal structure of a computationally optimized H5 influenza hemagglutininCrystal structure of a computationally optimized H5 influenza hemagglutinin
Structural highlights
Publication Abstract from PubMedInfluenza A virus is a leading cause of death worldwide. Viruses of the H5 subtype have the potential to induce high mortality, and no vaccines are currently available to protect against H5 influenza viruses in the event of an outbreak. Experimental vaccination with one clade 2 virus does not protect against other subclades. The computationally optimized broadly reactive (COBRA) methodology was previously used to generate a H5 hemagglutinin (HA) antigen (COBRA2) that elicited increased serological breadth against multiple clade 2 H5N1 influenza viruses. In this report, we structurally and antigenically characterized the COBRA2 HA antigen. We examined the biochemical characteristics of the COBRA2 protein and determined the protein is correctly cleaved, properly folded into a trimeric structure, and antigenically correct by probing with HA head- and stem-specific monoclonal antibodies (mAbs). We further probed the antigenicity by examining binding of a panel of H5 mouse mAbs to the COBRA2 antigen, as well as several other HA antigens. We determined the X-ray crystal structure of the COBRA2 HA antigen to 2.8â¯A and the protein was observed to be in the expected trimeric form. The COBRA2 HA was structurally similar to the naturally occurring H5 HA antigens and suggests the protein folds similar to known HA structures. Overall, our data allow us to formulate a hypothesis on the mechanism of increased breadth due to vaccination with the COBRA2 HA antigen, which is that the protein incorporates antigenic sites from numerous HA antigens, and elicits mAbs with limited breadth, but with diversity in targeted antigenic sites. Structural and antigenic characterization of a computationally-optimized H5 hemagglutinin influenza vaccine.,Bar-Peled Y, Huang J, Nunez IA, Pierce SR, Ecker JW, Ross TM, Mousa JJ Vaccine. 2019 Sep 24;37(41):6022-6029. doi: 10.1016/j.vaccine.2019.08.062. Epub , 2019 Aug 31. PMID:31481254[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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