UBIQUITIN C-TERMINAL HYDROLASE L3 COMPLEX WITH UBIQUITIN-BASED SUICIDE SUBSTRATE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 一种控制导致疟疾的恶性疟原虫的新方法瞄准了这种寄生虫的泛素-蛋白酶体途径，这是其生存所必需的。由于宿主对病原体的防御机制依赖于泛素-蛋白酶体系统在抗原提呈和膜转运调节中的作用，许多病毒和细菌编码作用于泛素-蛋白酶体途径的蛋白质，然而在寄生虫中几乎完全缺乏关于这一途径的数据。 结果表明，恶性疟原虫(PfUchL3)中的哺乳动物UchL3同源基因(PfUchL3)具有去泛素化和去核苷化活性。我们感兴趣的是确定PfUchL3的分子结构，并揭示泛素和NEDD8双重特异性的机制。为此，我们制备了PfUchL3与基于泛素的自杀底物UbVME之间的络合物的晶体。

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. A new approach to controlling malaria-causing Plasmodium falciparum aims at the parasite's ubiquitin-proteasome pathway which is essential for its survival. Since the host's defense mechanisms against pathogens rely on the ubiquitin-proteasome system in antigen presentation and in the regulation of membrane trafficking, many viruses and bacteria encode proteins that act on the ubiquitin-proteasome pathway, yet there is a near-complete lack of data on this pathway in parasites. It was shown that the mammalian UchL3 ortholog in Plasmodium falciparum (PfUchL3) possesses deubiquitinating as well as deNeddylating activity. We are interested in determining the molecular architecture of PfUchL3 and revealing the mechanisms for the dual specificity towards ubiquitin and NEDD8. To this end we prepared crystals of the complex between PfUchL3 and the ubiquitin based suicide substrate UbVME.