Muecke, Katrin and Paulus, Christina and Bernhardt, Katharina and Gerrer, Katrin and Schoen, Kathrin and Fink, Alina and Sauer, Eva-Maria and Asbach-Nitzsche, Alexandra and Harwardt, Thomas and Kieninger, Barbel and Kremer, Werner and Kalbitzer, Hans Robert and Nevels, Michael (2014) Human Cytomegalovirus Major Immediate Early 1 Protein Targets Host Chromosomes by Docking to the Acidic Pocket on the Nucleosome Surface. JOURNAL OF VIROLOGY, 88 (2). pp. 1228-1248. ISSN 0022-538X, 1098-5514
Full text not available from this repository. (Request a copy)Abstract
The 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 H3H4. 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 beta-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SARCOMA-ASSOCIATED HERPESVIRUS; CHROMATIN-TETHERING DOMAIN; LOW-MULTIPLICITY INFECTION; 86-KILODALTON IE2 PROTEIN; EARLY GENE-EXPRESSION; NUCLEAR ANTIGEN 1; MITOTIC CHROMOSOMES; VIRAL REPLICATION; ANGSTROM RESOLUTION; EARLY PROMOTER; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Nov 2019 13:50 |
| Last Modified: | 29 Nov 2019 13:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/11093 |
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