MCMV USP DOMAIN IN COMPLEX WITH AN 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。 单纯疱疹病毒1型(HSV-1)最大的被膜蛋白UL36含有一种新的脱泛素化活性。疱疹病毒科的所有成员都含有HSV-1 UL36同源物，其N末端片段显示出完美的催化残基保守。HSV-1、小鼠巨细胞病毒(MCMV)和EB病毒(EBV)的同源物在体外也显示出去泛素化活性。这一活动在所有亚家族中的保存表明了一种重要的功能，如果不是必要的话。为了深入了解疱疹病毒科病毒去泛素化活性的底物特异性和反应机制，我们旨在确定HSV-1 UL36的N末端片段以及具有这种新的去泛素化活性的MCMV和EBV的同源片段的三维结构。

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. The largest tegument protein of herpes simplex virus 1 (HSV-1), UL36, contains a novel deubiquitinating activity embedded in it. All members of the Herpesviridae contain a HSV-1 UL36homologue, the N-terminal segment of which show perfect conservation of putative catalytic residues. Homologs from HSV-1, murine cytomegalovirus (MCMV) and Epstein-Barr virus (EBV), chosen as representatives of the beta- and gammaherpesvirus subfamilies, respectively, were shown to display a deubiquitinating activity in vitro as well. The conservation of this activity throughout all subfamilies is indicative of an important, if not essential, function. In order to gain insights into substrate specificity and the reaction mechanism of the deubiquitinating activity of Herpesviridae, we aim to determine three-dimensional structures of N-terminal segments of HSV-1 UL36 and homologous segments of MCMV and EBV featuring this novel deubiquitinating activity.