Structure-based mechanism of action of a viral poly(ADP-ribose) polymerase 1-interacting protein facilitating virus replication
DC Field | Value | Language |
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dc.contributor.author | Chung, Woo-Chang | - |
dc.contributor.author | Kim, Junsoo | - |
dc.contributor.author | Kim, Byung Chul | - |
dc.contributor.author | Kang, Hye-Ri | - |
dc.contributor.author | Son, JongHyeon | - |
dc.contributor.author | Ki, Hosam | - |
dc.contributor.author | Hwang, Kwang Yeon | - |
dc.contributor.author | Song, Moon Jung | - |
dc.date.accessioned | 2021-09-02T04:12:29Z | - |
dc.date.available | 2021-09-02T04:12:29Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2018-11 | - |
dc.identifier.issn | 2052-2525 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/71962 | - |
dc.description.abstract | Poly(ADP-ribose) polymerase 1 (PARP-1), an enzyme that modifies nuclear proteins by poly(ADP-ribosyl) ation, regulates various cellular activities and restricts the lytic replication of oncogenic gammaherpesviruses by inhibiting the function of replication and transcription activator (RTA), a key switch molecule of the viral life cycle. A viral PARP-1-interacting protein (vPIP) encoded by murine gammaherpesvirus 68 (MHV-68) orf49 facilitates lytic replication by disrupting interactions between PARP-1 and RTA. Here, the structure of MHV-68 vPIP was determined at 2.2 angstrom resolution. The structure consists of 12 alpha-helices with characteristic N-terminal beta-strands (N beta) and forms a V-shaped-twist dimer in the asymmetric unit. Structure-based mutagenesis revealed that N beta and the alpha 1 helix (residues 2-26) are essential for the nuclear localization and function of vPIP; three residues were then identified (Phe5, Ser12 and Thr16) that were critical for the function of vPIP and its interaction with PARP-1. A recombinant MHV-68 harboring mutations of these three residues showed severely attenuated viral replication both in vitro and in vivo. Moreover, ORF49 of Kaposi's sarcoma-associated herpesvirus also directly interacted with PARP-1, indicating a conserved mechanism of action of vPIPs. The results elucidate the novel molecular mechanisms by which oncogenic gammaherpesviruses overcome repression by PARP-1 using vPIPs. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | INT UNION CRYSTALLOGRAPHY | - |
dc.subject | SARCOMA-ASSOCIATED HERPESVIRUS | - |
dc.subject | EPSTEIN-BARR-VIRUS | - |
dc.subject | ADP-RIBOSE POLYMERASE | - |
dc.subject | MURINE GAMMAHERPESVIRUS-68 | - |
dc.subject | ORF49 PROTEIN | - |
dc.subject | DNA-DAMAGE | - |
dc.subject | IN-VIVO | - |
dc.subject | INFECTION | - |
dc.subject | GENE | - |
dc.subject | REACTIVATION | - |
dc.title | Structure-based mechanism of action of a viral poly(ADP-ribose) polymerase 1-interacting protein facilitating virus replication | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Hwang, Kwang Yeon | - |
dc.contributor.affiliatedAuthor | Song, Moon Jung | - |
dc.identifier.doi | 10.1107/S2052252518013854 | - |
dc.identifier.scopusid | 2-s2.0-85056186175 | - |
dc.identifier.wosid | 000448982300023 | - |
dc.identifier.bibliographicCitation | IUCRJ, v.5, pp.866 - 879 | - |
dc.relation.isPartOf | IUCRJ | - |
dc.citation.title | IUCRJ | - |
dc.citation.volume | 5 | - |
dc.citation.startPage | 866 | - |
dc.citation.endPage | 879 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalResearchArea | Crystallography | - |
dc.relation.journalResearchArea | Materials Science | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.relation.journalWebOfScienceCategory | Crystallography | - |
dc.relation.journalWebOfScienceCategory | Materials Science, Multidisciplinary | - |
dc.subject.keywordPlus | SARCOMA-ASSOCIATED HERPESVIRUS | - |
dc.subject.keywordPlus | EPSTEIN-BARR-VIRUS | - |
dc.subject.keywordPlus | ADP-RIBOSE POLYMERASE | - |
dc.subject.keywordPlus | MURINE GAMMAHERPESVIRUS-68 | - |
dc.subject.keywordPlus | ORF49 PROTEIN | - |
dc.subject.keywordPlus | DNA-DAMAGE | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | INFECTION | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | REACTIVATION | - |
dc.subject.keywordAuthor | viral PARP-1-interacting protein | - |
dc.subject.keywordAuthor | open reading frame 49 | - |
dc.subject.keywordAuthor | poly(ADP-ribose) polymerase 1 | - |
dc.subject.keywordAuthor | murine gammaherpesvirus 68 | - |
dc.subject.keywordAuthor | Kaposi&apos | - |
dc.subject.keywordAuthor | s sarcoma-associated herpesvirus | - |
dc.subject.keywordAuthor | structure determination | - |
dc.subject.keywordAuthor | X-ray crystallography | - |
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