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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们建议用溶液X射线散射法研究炭疽毒素保护性抗原(PA)和致死因子(LF)的溶液结构，以补充我们的结晶学研究。PA有一个柔性环，它在宿主细胞膜上形成一个附着孔，但这个环在我们的晶体结构中是看不见的。我们希望确定PA的低分辨结构，并通过将晶体结构与溶液结构相匹配来可视化环。还将研究PA环的与pH有关的孔形成。我们还计划研究溶液中的LF，以补充我们对PA和LF形成络合物时获得毒性所必需的LF构象变化的结晶学研究。最后，我们希望研究PA-LF络合物的溶液结构，因为我们对LF和PA如何相互作用知之甚少。

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.