4U6V

Mechanisms of Neutralization of a Human Anti-Alpha Toxin Antibody

Summary for 4U6V

• Entry DOI: 10.2210/pdb4u6v/pdb
• Descriptor: Fab, antigen binding fragment, heavy chain, Fab, antigen binding fragment, light chain, Alpha-hemolysin, ... (5 entities in total)
• Functional Keywords: alpha toxin, fab, staphylococcus aureus, mutagenesis, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Secreted : Q2G1X0
• Total number of polymer chains: 6
• Total formula weight: 161577.53

Authors

Oganesyan, V.Y.,Peng, L.,Damschroder, M.M.,Cheng, L.,Sadowska, A.,Tkaczyk, C.,Sellman, B.,Wu, H.,Dall'Acqua, W.F. (deposition date: 2014-07-29, release date: 2014-09-17, Last modification date: 2024-11-20)

Primary citation

Oganesyan, V.,Peng, L.,Damschroder, M.M.,Cheng, L.,Sadowska, A.,Tkaczyk, C.,Sellman, B.R.,Wu, H.,Dall'Acqua, W.F.
Mechanisms of Neutralization of a Human Anti-alpha-toxin Antibody.
J.Biol.Chem., 289:29874-29880, 2014

PubMed Abstract: MEDI4893 is a neutralizing human monoclonal antibody that targets α-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 Å and further characterized its epitope using various engineered AT variants. We have found that MEDI4893 recognizes a novel epitope in the so-called "rim" domain of AT and exerts its neutralizing effect through a dual mechanism. In particular, MEDI4893 not only sterically blocks binding of AT to its cell receptor but also prevents it from adopting a lytic heptameric trans-membrane conformation.

PubMed: 25210036
DOI: 10.1074/jbc.M114.601328

Experimental method

X-RAY DIFFRACTION (2.56 Å)