{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T21:29:40Z","timestamp":1777670980710,"version":"3.51.4"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"21","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Immediate early proteins of human herpesvirus 6A (HHV-6A) are expressed at the outset of lytic infection and thereby regulate viral gene expression. Immediate early protein 2 (IE2) of HHV-6A is a transactivator that drives a variety of promoters. The C-terminal region of HHV-6A IE2 is shared among IE2 homologs in betaherpesviruses and is involved in dimerization, DNA binding, and transcription factor binding. In this study, the structure of the IE2 C-terminal domain (IE2-CTD) was determined by X-ray crystallography at a resolution of 2.5 \u212b. IE2-CTD forms a homodimer stabilized by a \u03b2-barrel core with two interchanging long loops. Unexpectedly, the core structure resembles those of the gammaherpesvirus factors EBNA1 of Epstein-Barr virus and LANA of Kaposi sarcoma-associated herpesvirus, but the interchanging loops are longer in IE2-CTD and form helix-turn-helix (HTH)-like motifs at their tips. The HTH and surrounding \u03b1-helices form a structural feature specific to the IE2 group. The apparent DNA-binding site (based on structural similarity with EBNA1 and LANA) resides on the opposite side of the HTH-like motifs, surrounded by positive electrostatic potential. Mapping analysis of conserved residues on the three-dimensional structure delineated a potential factor-binding site adjacent to the expected DNA-binding site. The predicted bi- or tripartite functional sites indicate a role for IE2-CTD as an adapter connecting the promoter and transcriptional factors that drive gene expression.<\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Human herpesvirus 6A (HHV-6A) and HHV-6B belong to betaherpesvirus subfamily. Both viruses establish lifelong latency after primary infection, and their reactivation poses a significant risk to immunocompromised patients. Immediate early protein 2 (IE2) of HHV-6A and HHV-6B is a transactivator that triggers viral replication and contains a DNA-binding domain shared with other betaherpesviruses such as human herpesvirus 7 and human cytomegalovirus. In this study, an atomic structure of the DNA-binding domain of HHV-6A IE2 was determined and analyzed, enabling a structure-based understanding of the functions of IE2, specifically DNA recognition and interaction with transcription factors. Unexpectedly, the dimeric core resembles the DNA-binding domain of transcription regulators from gammaherpesviruses, showing structural conservation as a DNA-binding domain but with its own unique structural features. These findings facilitate further characterization of this key viral transactivator.\n          <\/jats:p>","DOI":"10.1128\/jvi.01121-17","type":"journal-article","created":{"date-parts":[[2017,8,10]],"date-time":"2017-08-10T00:50:35Z","timestamp":1502326235000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Crystal Structure of the DNA-Binding Domain of Human Herpesvirus 6A Immediate Early Protein 2"],"prefix":"10.1128","volume":"91","author":[{"given":"Mitsuhiro","family":"Nishimura","sequence":"first","affiliation":[{"name":"Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aika","family":"Wakata","sequence":"additional","affiliation":[{"name":"Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kento","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuko","family":"Mori","sequence":"additional","affiliation":[{"name":"Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2010.02.014"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-013-1902-5"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-012-1299-6"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.29.2.367-372.1991"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-74-10-2257"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/1348-0421.12110"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2009.01312.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01606-15"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1305187110"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01447-14"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/162.4.852"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(88)91893-4"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2010.08.002"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.4065\/mcp.2010.0350"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2015.76"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13365-016-0473-0"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6822(03)00007-2"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1995.1228"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.10.8053-8063.1999"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.5.2978-2985.1994"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1994.1589"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1702(02)00126-0"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.10.6201-6214.1993"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.06.030"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.4.1870-1878.2001"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(98)00056-0"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.8.4981-4991.1993"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-74-12-2691"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.7.4452-4456.1992"},{"key":"e_1_3_2_31_2","first-page":"E142","article-title":"Purification, crystallization and X-ray diffraction study of the C-terminal domain of human herpesvirus 6A immediate early protein 2","volume":"62","author":"Wang J","year":"2017","unstructured":"Wang J Nishimura M Wakata A Mori Y . 2017. Purification, crystallization and X-ray diffraction study of the C-terminal domain of human herpesvirus 6A immediate early protein 2. Kobe J Med Sci62:E142\u2013E149.","journal-title":"Kobe J Med Sci"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm993"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90232-5"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003672"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)94115-3"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-8-9"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2012.09.005"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.6064\/2012\/438204"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.3390\/v6124961"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.2260"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/359505a0"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.2247"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1421804112"},{"key":"e_1_3_2_44_2","volume-title":"Molecular biology of the cell","author":"Alberts B","year":"2002","unstructured":"Alberts B . 2002. Molecular biology of the cell, 4th ed. Garland Science, New York, NY.","edition":"4"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05315-11"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06584.x"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909052925"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909012098"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444912001308"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(96)00009-4"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005594"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(91)90434-D"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0137420"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.15.7969-7983.2004"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.9.4609-4616.2004"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.75"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01121-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01121-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T14:24:59Z","timestamp":1646490299000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.01121-17"}},"subtitle":[],"editor":[{"given":"Rozanne M.","family":"Sandri-Goldin","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2017,11]]},"references-count":57,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1128\/JVI.01121-17"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01121-17","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11]]},"assertion":[{"value":"2017-07-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-07-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-10-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01121-17"}}