Structural highlights
Function
[HLA_STAA8] Alpha-toxin binds to the membrane of eukaryotic cells resulting in the release of low-molecular weight molecules and leading to an eventual osmotic lysis. Heptamer oligomerization and pore formation is required for lytic activity (By similarity).
Publication Abstract from PubMed
MEDI4893 is a neutralizing human monoclonal antibody that targets alpha toxin (AT), and is currently undergoing evaluation in the field of Staphylococcus aureus-mediated diseases. We have solved the crystal structure of MEDI4893 Fab bound to monomeric AT at a resolution of 2.56 A, and further characterized its epitope using various engineered AT variants. We have found that MEDI4893 recognizes a novel epitope in AT so-called rim domain, and exerts its neutralizing effect through a dual mechanism. More particularly, MEDI4893 not only sterically blocks binding of AT to its cell receptor, but also prevents it from adopting a lytic heptameric trans-membrane conformation.
Mechanisms of Neutralization of a Human Anti-Alpha Toxin Antibody.,Oganesyan V, Peng L, Damschroder MM, Cheng L, Sadowska A, Tkaczyk C, Sellman BR, Wu H, Dall'Acqua WF J Biol Chem. 2014 Sep 10. pii: jbc.M114.601328. PMID:25210036[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Oganesyan V, Peng L, Damschroder MM, Cheng L, Sadowska A, Tkaczyk C, Sellman BR, Wu H, Dall'Acqua WF. Mechanisms of Neutralization of a Human Anti-Alpha Toxin Antibody. J Biol Chem. 2014 Sep 10. pii: jbc.M114.601328. PMID:25210036 doi:http://dx.doi.org/10.1074/jbc.M114.601328
