Summary for 6A4V
| Entry DOI | 10.2210/pdb6a4v/pdb |
| Descriptor | 49 protein (2 entities in total) |
| Functional Keywords | gamma herpesvirus 68 open reading frame 49, orf49 poly (adp-ribose) polymerase-1 (parp-1), replication |
| Biological source | Murid herpesvirus 4 (MuHV-4) |
| Total number of polymer chains | 2 |
| Total formula weight | 76403.61 |
| Authors | Hwang, K.Y.,Song, M.J.,Kim, J.S.,Cheong, W.C. (deposition date: 2018-06-21, release date: 2019-06-26, Last modification date: 2024-03-27) |
| Primary citation | Chung, W.C.,Kim, J.,Kim, B.C.,Kang, H.R.,Son, J.,Ki, H.,Hwang, K.Y.,Song, M.J. Structure-based mechanism of action of a viral poly(ADP-ribose) polymerase 1-interacting protein facilitating virus replication. Iucrj, 5:866-879, 2018 Cited by PubMed 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) facilitates lytic replication by disrupting interactions between PARP-1 and RTA. Here, the structure of MHV-68 vPIP was determined at 2.2 Å resolution. The structure consists of 12 α-helices with characteristic N-terminal β-strands (Nβ) and forms a V-shaped-twist dimer in the asymmetric unit. Structure-based mutagenesis revealed that Nβ and the α1 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 and . 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. PubMed: 30443370DOI: 10.1107/S2052252518013854 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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