5u1b: Difference between revisions
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==Ferritin with Gc MtrE loop2 inserted at the N-terminus== | |||
<StructureSection load='5u1b' size='340' side='right' caption='[[5u1b]], [[Resolution|resolution]] 2.81Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5u1b]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U1B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U1B FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5u1a|5u1a]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Bacterial_non-heme_ferritin Bacterial non-heme ferritin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.16.3.2 1.16.3.2] </span></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=5u1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u1b OCA], [http://pdbe.org/5u1b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u1b RCSB], [http://www.ebi.ac.uk/pdbsum/5u1b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u1b ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Effective vaccines are urgently needed to combat gonorrhea, a common sexually transmitted bacterial infection, for which treatment options are diminishing due to rapid emergence of antibiotic resistance. We have used a rational approach to the development of gonorrhea vaccines, and genetically engineered nanoparticles to present antigenic peptides of Neisseria gonorrhoeae, the causative agent of gonorrhea. We hypothesized that the ferritin nanocage could be used as a platform to display an ordered array of N. gonorrhoeae antigenic peptides on its surface. MtrE, the outer membrane channel of the highly conserved gonococcal MtrCDE active efflux pump, is an attractive vaccine target due to its importance in protecting N. gonorrhoeae from host innate effectors and antibiotic resistance. Using computational approaches, we designed constructs that expressed chimeric proteins of the Helicobacter pylori ferritin and antigenic peptides that correspond to the two surface-exposed loops of N. gonorrhoeae MtrE. The peptides were inserted at the N terminus or in a surface-exposed ferritin loop between helices alphaA and alphaB. Crystal structures of the chimeric proteins revealed that the proteins assembled correctly into a 24-mer nanocage structure. Although the inserted N. gonorrhoeae peptides were disordered, it was clear that they were displayed on the nanocage surface, but with multiple conformations. Our results confirmed that the ferritin nanoparticle is a robust platform to present antigenic peptides and therefore an ideal system for rational design of immunogens. | |||
Structure-based design of ferritin nanoparticle immunogens displaying antigenic loops of Neisseria gonorrhoeae.,Wang L, Xing D, Le Van A, Jerse AE, Wang S FEBS Open Bio. 2017 Jul 24;7(8):1196-1207. doi: 10.1002/2211-5463.12267., eCollection 2017 Aug. PMID:28781959<ref>PMID:28781959</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5u1b" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bacterial non-heme ferritin]] | |||
[[Category: Wang, S]] | |||
[[Category: 24mer cage]] | |||
[[Category: Chimera]] | |||
[[Category: Immunogen]] | |||
[[Category: Nanoparticle]] | |||
[[Category: Oxidoreductase]] | |||
Revision as of 09:48, 11 October 2017
Ferritin with Gc MtrE loop2 inserted at the N-terminusFerritin with Gc MtrE loop2 inserted at the N-terminus
Structural highlights
Publication Abstract from PubMedEffective vaccines are urgently needed to combat gonorrhea, a common sexually transmitted bacterial infection, for which treatment options are diminishing due to rapid emergence of antibiotic resistance. We have used a rational approach to the development of gonorrhea vaccines, and genetically engineered nanoparticles to present antigenic peptides of Neisseria gonorrhoeae, the causative agent of gonorrhea. We hypothesized that the ferritin nanocage could be used as a platform to display an ordered array of N. gonorrhoeae antigenic peptides on its surface. MtrE, the outer membrane channel of the highly conserved gonococcal MtrCDE active efflux pump, is an attractive vaccine target due to its importance in protecting N. gonorrhoeae from host innate effectors and antibiotic resistance. Using computational approaches, we designed constructs that expressed chimeric proteins of the Helicobacter pylori ferritin and antigenic peptides that correspond to the two surface-exposed loops of N. gonorrhoeae MtrE. The peptides were inserted at the N terminus or in a surface-exposed ferritin loop between helices alphaA and alphaB. Crystal structures of the chimeric proteins revealed that the proteins assembled correctly into a 24-mer nanocage structure. Although the inserted N. gonorrhoeae peptides were disordered, it was clear that they were displayed on the nanocage surface, but with multiple conformations. Our results confirmed that the ferritin nanoparticle is a robust platform to present antigenic peptides and therefore an ideal system for rational design of immunogens. Structure-based design of ferritin nanoparticle immunogens displaying antigenic loops of Neisseria gonorrhoeae.,Wang L, Xing D, Le Van A, Jerse AE, Wang S FEBS Open Bio. 2017 Jul 24;7(8):1196-1207. doi: 10.1002/2211-5463.12267., eCollection 2017 Aug. PMID:28781959[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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