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 structura...
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MDPI AG
2015-08-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/7/8/2834 |
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| author | Mirjam Steingruber Eileen Socher Corina Hutterer Rike Webel Tim Bergbrede Tihana Lenac Heinrich Sticht Manfred Marschall |
| author_facet | Mirjam Steingruber Eileen Socher Corina Hutterer Rike Webel Tim Bergbrede Tihana Lenac Heinrich Sticht Manfred Marschall |
| author_sort | Mirjam Steingruber |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T06:05:31Z |
| format | Article |
| id | doaj.art-647ceed51f324be99b715bd3825e9f95 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-13T06:05:31Z |
| publishDate | 2015-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-647ceed51f324be99b715bd3825e9f952022-12-21T23:57:13ZengMDPI AGViruses1999-49152015-08-01784582460110.3390/v7082834v7082834The Interaction between Cyclin B1 and Cytomegalovirus Protein Kinase pUL97 is Determined by an Active Kinase DomainMirjam Steingruber0Eileen Socher1Corina Hutterer2Rike Webel3Tim Bergbrede4Tihana Lenac5Heinrich Sticht6Manfred Marschall7Institute for Clinical and Molecular Virology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDivision of Bioinformatics, Institute of Biochemistry, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyInstitute for Clinical and Molecular Virology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyInstitute for Clinical and Molecular Virology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyLead Discovery Center GmbH, 44227 Dortmund, GermanyDepartment of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, CroatiaDivision of Bioinformatics, Institute of Biochemistry, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyInstitute for Clinical and Molecular Virology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyReplication 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.http://www.mdpi.com/1999-4915/7/8/2834human cytomegalovirusprotein kinase pUL97CDK orthologcyclin Bprotein-protein interactionkinase activitymode of kinase-cyclin interactionactive conformation |
| spellingShingle | Mirjam Steingruber Eileen Socher Corina Hutterer Rike Webel Tim Bergbrede Tihana Lenac Heinrich Sticht Manfred Marschall The Interaction between Cyclin B1 and Cytomegalovirus Protein Kinase pUL97 is Determined by an Active Kinase Domain Viruses human cytomegalovirus protein kinase pUL97 CDK ortholog cyclin B protein-protein interaction kinase activity mode of kinase-cyclin interaction active conformation |
| title | The Interaction between Cyclin B1 and Cytomegalovirus Protein Kinase pUL97 is Determined by an Active Kinase Domain |
| title_full | The Interaction between Cyclin B1 and Cytomegalovirus Protein Kinase pUL97 is Determined by an Active Kinase Domain |
| title_fullStr | The Interaction between Cyclin B1 and Cytomegalovirus Protein Kinase pUL97 is Determined by an Active Kinase Domain |
| title_full_unstemmed | The Interaction between Cyclin B1 and Cytomegalovirus Protein Kinase pUL97 is Determined by an Active Kinase Domain |
| title_short | The Interaction between Cyclin B1 and Cytomegalovirus Protein Kinase pUL97 is Determined by an Active Kinase Domain |
| title_sort | interaction between cyclin b1 and cytomegalovirus protein kinase pul97 is determined by an active kinase domain |
| topic | human cytomegalovirus protein kinase pUL97 CDK ortholog cyclin B protein-protein interaction kinase activity mode of kinase-cyclin interaction active conformation |
| url | http://www.mdpi.com/1999-4915/7/8/2834 |
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