Journal Article

The Interaction between Cyclin B1 and Cytomegalovirus Protein Kinase pUL97 is Determined by an Active Kinase Domain

Socher, Eileen, Bergbrede, Tim, Sticht, Heinrich, Steingruber, Mirjam, Lenac, Tihana, Webel, Rike, Marschall, Manfred, Hutterer, Corina

2015

Overview

Replication of human cytomegalovirus (HCMV) is characterized by a tight virus-host cell interaction. Cyclin-dependent protein kinases (CDKs) are functionally integrated into viral gene expression and protein modification. The HCMV-encoded protein kinase pUL97 acts as a CDK ortholog showing structural and functional similarities. Recently, we reported an interaction between pUL97 kinase with a subset of host cyclins, in particular with cyclin T1. Here, we describe an interaction of pUL97 at an even higher affinity with cyclin B1. As a striking feature, the interaction between pUL97 and cyclin B1 proved to be strictly dependent on pUL97 activity, as interaction could be abrogated by treatment with pUL97 inhibitors or by inserting mutations into the conserved kinase domain or the nonconserved C-terminus of pUL97, both producing loss of activity. Thus, we postulate that the mechanism of pUL97-cyclin B1 interaction is determined by an active pUL97 kinase domain.

• Publisher: MDPI AG,MDPI
• Subject: active conformation / Amino acids / Binding Sites / Catalytic Domain / CDK ortholog / Cell cycle / Cells, Cultured / cyclin B / Cyclin B1 - metabolism / Cyclin-dependent kinases / Cytomegalovirus / Cytomegalovirus - physiology / DNA Mutational Analysis / Drug resistance / Electronic mail systems / Host-Pathogen Interactions / Human cytomegalovirus / Humans / kinase activity / Kinases / mode of kinase-cyclin interaction / Phosphotransferases (Alcohol Group Acceptor) - metabolism / Protein Binding / Protein Interaction Mapping / protein kinase pUL97 / protein-protein interaction / Proteins / RNA polymerase / Virus Replication / Viruses