dc.contributor.author |
Radjainia, Mazdak |
en |
dc.contributor.author |
Hyun, Jae |
en |
dc.contributor.author |
Leysath, CE |
en |
dc.contributor.author |
Leppla, SH |
en |
dc.contributor.author |
Mitra, Alok |
en |
dc.date.accessioned |
2012-03-07T23:14:57Z |
en |
dc.date.issued |
2010-08-10 |
en |
dc.identifier.citation |
P NATL ACAD SCI USA 107(32):14070-14074 10 Aug 2010 |
en |
dc.identifier.issn |
0027-8424 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/13370 |
en |
dc.description.abstract |
The tripartite protein exotoxin secreted by Bacillus anthracis, a major contributor to its virulence and anthrax pathogenesis, consists of binary complexes of the protective antigen (PA) heptamer (PA63h), produced by proteolytic cleavage of PA, together with either lethal factor or edema factor. The mouse monoclonal anti- PA antibody 1G3 was previously shown to be a potent antidote that shares FC domain dependency with the human monoclonal antibody MDX-1303 currently under clinical development. Here we demonstrate that 1G3 instigates severe perturbation of the PA63h structure and creates a PA supercomplex as visualized by electron microscopy. This phenotype, produced by the unconventional mode of antibody action, highlights the feasibility for optimization of vaccines based on analogous structural modification of PA63h as an additional strategy for future remedies against anthrax. |
en |
dc.language |
EN |
en |
dc.publisher |
NATL ACAD SCIENCES |
en |
dc.relation.ispartofseries |
PNAS: Proceedings of the National Academy of Sciences of the United States of America |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/1091-6490/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
anthrax toxin |
en |
dc.subject |
neutralizing antibody 1G3 |
en |
dc.subject |
passive immunization |
en |
dc.subject |
protein therapeutics |
en |
dc.subject |
single-particle analysis |
en |
dc.subject |
BACILLUS-ANTHRACIS |
en |
dc.subject |
CRYSTAL-STRUCTURE |
en |
dc.subject |
LETHAL FACTOR |
en |
dc.subject |
MONOCLONAL-ANTIBODIES |
en |
dc.subject |
ELECTRON-MICROSCOPY |
en |
dc.subject |
CELL-RECEPTOR |
en |
dc.subject |
PROPHYLAXIS |
en |
dc.subject |
COMPONENT |
en |
dc.subject |
BINDING |
en |
dc.title |
Anthrax toxin-neutralizing antibody reconfigures the protective antigen heptamer into a supercomplex |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1073/pnas.1006473107 |
en |
pubs.issue |
32 |
en |
pubs.begin-page |
14070 |
en |
pubs.volume |
107 |
en |
dc.rights.holder |
Copyright: NATL ACAD SCIENCES |
en |
dc.identifier.pmid |
20660775 |
en |
pubs.author-url |
http://www.pnas.org/content/107/32/14070 |
en |
pubs.end-page |
14074 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
120061 |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Biological Sciences |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
dc.identifier.eissn |
1091-6490 |
en |
pubs.record-created-at-source-date |
2012-02-09 |
en |
pubs.dimensions-id |
20660775 |
en |