The Interaction between Cyclin B1 and Cytomegalovirus Protein Kinase pUL97 is Determined by an Active Kinase Domain.
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.
Institute for Clinical and Molecular Virology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany. mirjam.steingruber@viro.med.uni-erlangen.de.
Mirjam
M
Steingruber
Division of Bioinformatics, Institute of Biochemistry, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany. eileen.socher@fau.de.
Eileen
E
Socher
Institute for Clinical and Molecular Virology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany. corina.hutterer@viro.med.uni-erlangen.de.
Corina
C
Hutterer
Institute for Clinical and Molecular Virology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany. rike.webel@viro.med.uni-erlangen.de.
Rike
R
Webel
Lead Discovery Center GmbH, 44227 Dortmund, Germany. bergbrede@lead-discovery.de.
Tim
T
Bergbrede
Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia. tihana.lenac@medri.uniri.hr.
Tihana
T
Lenac
Division of Bioinformatics, Institute of Biochemistry, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany. heinrich.sticht@fau.de.
Heinrich
H
Sticht
Institute for Clinical and Molecular Virology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany. manfred.marschall@viro.med.uni-erlangen.de.
Manfred
M
Marschall
D001665:Binding Sites; D020134:Catalytic Domain; D002478:Cells, Cultured; D056744:Cyclin B1 / Q000378:metabolism*; D003587:Cytomegalovirus / Q000502:physiology*; D004252:DNA Mutational Analysis; D054884:Host-Pathogen Interactions; D006801:Humans; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D014779:Virus Replication
D056744:Cyclin B1; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase
CDK ortholog; active conformation; cyclin B; human cytomegalovirus; kinase activity; mode of kinase-cyclin interaction; protein kinase pUL97; protein-protein interaction