MCMV USP DOMAIN IN COMPLEX WITH AN UBIQUITIN-BASED SUICIDE SUBSTRATE

这个子项目是众多研究子项目之一

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.