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''' | ==Structure-based energetics of protein interfaces guide Foot-and-Mouth disease virus vaccine design== | ||
<StructureSection load='5ac9' size='340' side='right' caption='[[5ac9]], [[Resolution|resolution]] 3.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ac9]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AC9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AC9 FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5aca|5aca]]</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=5ac9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ac9 OCA], [http://pdbe.org/5ac9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ac9 RCSB], [http://www.ebi.ac.uk/pdbsum/5ac9 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Virus capsids are primed for disassembly, yet capsid integrity is key to generating a protective immune response. Foot-and-mouth disease virus (FMDV) capsids comprise identical pentameric protein subunits held together by tenuous noncovalent interactions and are often unstable. Chemically inactivated or recombinant empty capsids, which could form the basis of future vaccines, are even less stable than live virus. Here we devised a computational method to assess the relative stability of protein-protein interfaces and used it to design improved candidate vaccines for two poorly stable, but globally important, serotypes of FMDV: O and SAT2. We used a restrained molecular dynamics strategy to rank mutations predicted to strengthen the pentamer interfaces and applied the results to produce stabilized capsids. Structural analyses and stability assays confirmed the predictions, and vaccinated animals generated improved neutralizing-antibody responses to stabilized particles compared to parental viruses and wild-type capsids. | |||
Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design.,Kotecha A, Seago J, Scott K, Burman A, Loureiro S, Ren J, Porta C, Ginn HM, Jackson T, Perez-Martin E, Siebert CA, Paul G, Huiskonen JT, Jones IM, Esnouf RM, Fry EE, Maree FF, Charleston B, Stuart DI Nat Struct Mol Biol. 2015 Sep 21. doi: 10.1038/nsmb.3096. PMID:26389739<ref>PMID:26389739</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5ac9" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Burman, A]] | [[Category: Burman, A]] | ||
[[Category: | [[Category: Charleston, B]] | ||
[[Category: | [[Category: Esnouf, R M]] | ||
[[Category: | [[Category: Fry, E E]] | ||
[[Category: | [[Category: Ginn, H M]] | ||
[[Category: | [[Category: Huiskonen, J T]] | ||
[[Category: | [[Category: Jackson, T]] | ||
[[Category: Jones, I M]] | |||
[[Category: Kotecha, A]] | [[Category: Kotecha, A]] | ||
[[Category: Loureiro, S]] | [[Category: Loureiro, S]] | ||
[[Category: Maree, F F]] | |||
[[Category: Paul, G]] | [[Category: Paul, G]] | ||
[[Category: PerezMartin, E]] | |||
[[Category: Porta, C]] | |||
[[Category: Ren, J]] | |||
[[Category: Scott, K]] | [[Category: Scott, K]] | ||
[[Category: | [[Category: Seago, J]] | ||
[[Category: | [[Category: Siebert, C A]] | ||
[[Category: Stuart, D | [[Category: Stuart, D I]] | ||
[[Category: | [[Category: Fmdv]] | ||
[[Category: | [[Category: Foot and mouth disease virus]] | ||
[[Category: Vaccine]] | |||
[[Category: Virus]] | |||
Revision as of 11:05, 30 September 2015
Structure-based energetics of protein interfaces guide Foot-and-Mouth disease virus vaccine designStructure-based energetics of protein interfaces guide Foot-and-Mouth disease virus vaccine design
Structural highlights
Publication Abstract from PubMedVirus capsids are primed for disassembly, yet capsid integrity is key to generating a protective immune response. Foot-and-mouth disease virus (FMDV) capsids comprise identical pentameric protein subunits held together by tenuous noncovalent interactions and are often unstable. Chemically inactivated or recombinant empty capsids, which could form the basis of future vaccines, are even less stable than live virus. Here we devised a computational method to assess the relative stability of protein-protein interfaces and used it to design improved candidate vaccines for two poorly stable, but globally important, serotypes of FMDV: O and SAT2. We used a restrained molecular dynamics strategy to rank mutations predicted to strengthen the pentamer interfaces and applied the results to produce stabilized capsids. Structural analyses and stability assays confirmed the predictions, and vaccinated animals generated improved neutralizing-antibody responses to stabilized particles compared to parental viruses and wild-type capsids. Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design.,Kotecha A, Seago J, Scott K, Burman A, Loureiro S, Ren J, Porta C, Ginn HM, Jackson T, Perez-Martin E, Siebert CA, Paul G, Huiskonen JT, Jones IM, Esnouf RM, Fry EE, Maree FF, Charleston B, Stuart DI Nat Struct Mol Biol. 2015 Sep 21. doi: 10.1038/nsmb.3096. PMID:26389739[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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