Walters Matthew S, Kyratsous Christos A, Silverstein Saul J
Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, 701 W. 168th St., New York, NY 10032, USA.
J Virol. 2010 Jul;84(13):6861-5. doi: 10.1128/JVI.00335-10. Epub 2010 Apr 14.
Varicella zoster virus encodes an immediate-early (IE) protein termed ORF61p that is orthologous to the herpes simplex virus IE protein ICP0. Although these proteins share several functional properties, ORF61p does not fully substitute for ICP0. The greatest region of similarity between these proteins is a RING finger domain. We demonstrate that disruption of the ORF61p RING finger domain by amino acid substitution (Cys19Gly) alters ORF61p intranuclear distribution and abolishes ORF61p-mediated dispersion of Sp100-containing nuclear bodies. In addition, we demonstrate that an intact ORF61p RING finger domain is necessary for E3 ubiquitin ligase activity and is required for autoubiquitination and regulation of protein stability.
水痘带状疱疹病毒编码一种即刻早期(IE)蛋白,称为ORF61p,它与单纯疱疹病毒的IE蛋白ICP0是直系同源的。尽管这些蛋白具有若干功能特性,但ORF61p并不能完全替代ICP0。这些蛋白之间最大的相似区域是一个环状结构域。我们证明,通过氨基酸取代(Cys19Gly)破坏ORF61p环状结构域会改变ORF61p在细胞核内的分布,并消除ORF61p介导的含Sp100的核体的分散。此外,我们证明完整的ORF61p环状结构域对于E3泛素连接酶活性是必需的,并且是自身泛素化和蛋白质稳定性调节所必需的。