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dc.contributor.authorMücke, Katrin
dc.contributor.authorPaulus, Christina
dc.contributor.authorBernhardt, Katharina
dc.contributor.authorGerrer, Katrin
dc.contributor.authorSchön, Kathrin
dc.contributor.authorFink, Alina
dc.contributor.authorSauer, Eva-Maria
dc.contributor.authorAsbach-Nitzsche, Alexandra
dc.contributor.authorHarwardt, Thomas
dc.contributor.authorKieninger, Bärbel
dc.contributor.authorKremer, Werner
dc.contributor.authorKalbitzer, Hans Robert
dc.contributor.authorNevels, Michael
dc.identifier.citationMücke , K , Paulus , C , Bernhardt , K , Gerrer , K , Schön , K , Fink , A , Sauer , E-M , Asbach-Nitzsche , A , Harwardt , T , Kieninger , B , Kremer , W , Kalbitzer , H R & Nevels , M 2014 , ' Human cytomegalovirus major immediate early 1 protein targets host chromosomes by docking to the acidic pocket on the nucleosome surface ' , Journal of Virology , vol. 88 , no. 2 , pp. 1228-1248 .
dc.identifier.otherPURE: 173809775
dc.identifier.otherPURE UUID: ff54ae23-309b-49e8-b91c-8a937ad68f22
dc.identifier.otherPubMed: 24227840
dc.identifier.otherScopus: 84891707336
dc.identifier.otherORCID: /0000-0002-7115-407X/work/28624008
dc.identifier.otherORCID: /0000-0002-4123-5629/work/47136648
dc.description.abstractThe 72-kDa immediate early 1 (IE1) protein encoded by human cytomegalovirus (hCMV) is a nuclearly localized promiscuous regulator of viral and cellular transcription. IE1 has long been known to associate with host mitotic chromatin, yet the mechanisms underlying this interaction have not been specified. In this study, we identify the cellular chromosome receptor for IE1. We demonstrate that the viral protein targets human nucleosomes by directly binding to core histones in a nucleic acid-independent manner. IE1 exhibits two separable histone-interacting regions with differential binding specificities for H2A-H2B and H3-H4. The H2A-H2B binding region was mapped to an evolutionarily conserved 10-amino-acid motif within the chromatin-tethering domain (CTD) of IE1. Results from experimental approaches combined with molecular modeling indicate that the IE1 CTD adopts a β-hairpin structure, docking with the acidic pocket formed by H2A-H2B on the nucleosome surface. IE1 binds to the acidic pocket in a way similar to that of the latency-associated nuclear antigen (LANA) of the Kaposi's sarcoma-associated herpesvirus. Consequently, the IE1 and LANA CTDs compete for binding to nucleosome cores and chromatin. Our work elucidates in detail how a key viral regulator is anchored to human chromosomes and identifies the nucleosomal acidic pocket as a joint target of proteins from distantly related viruses. Based on the striking similarities between the IE1 and LANA CTDs and the fact that nucleosome targeting by IE1 is dispensable for productive replication even in "clinical" strains of hCMV, we speculate that the two viral proteins may serve analogous functions during latency of their respective viruses.
dc.relation.ispartofJournal of Virologyen
dc.rights© 2014, American Society for Microbiology. This work has been made available online in accordance with the publisher’s policies. This is the author created accepted version manuscript following peer review and as such may differ slightly from the final published version. The final published version of this work is available at
dc.subjectAmino acid sequenceen
dc.subjectBinding sitesen
dc.subjectChromosomes, humanen
dc.subjectCytomegalovirus infectionsen
dc.subjectImmediate-early proteinsen
dc.subjectModels, molecularen
dc.subjectMolecular sequence dataen
dc.subjectProtein bindingen
dc.subjectProtein structure, tertiaryen
dc.subjectQH301 Biologyen
dc.titleHuman cytomegalovirus major immediate early 1 protein targets host chromosomes by docking to the acidic pocket on the nucleosome surfaceen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.description.statusPeer revieweden

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