SAXS STUDIES OF THE ANTHRAX TOXIN PROTECTIVE ANTIGEN, LETHAL FACTOR AND THEIR CO

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose to study solution structure of anthrax toxin protective antigen (PA) and lethal factor (LF) by solution x-ray scattering to complement our crystallographic studies. PA has a flexible loop which forms an attachment pore to host cell membrane, but the loop is invisible in our crystal structure. We wish to determine the low resolution structure of PA and visualize the loop by fitting the crystal structure into the solution structure. The pH-dependent pore formation of the PA loop will also be studied. We also plan on studying LF in solution to complement our crystallographic studies on the conformational change of LF essential for acquiring toxicity when PA and LF forms a complex. Finally, we wish to study the solution structure of PA-LF complex as very little is know about how LF and PA interact.