4J4V
Pentameric SFTSVN with suramin
Summary for 4J4V
| Entry DOI | 10.2210/pdb4j4v/pdb |
| Descriptor | Nucleocapsid protein, 8,8'-[CARBONYLBIS[IMINO-3,1-PHENYLENECARBONYLIMINO(4-METHYL-3,1-PHENYLENE)CARBONYLIMINO]]BIS-1,3,5-NAPHTHALENETRISULFON IC ACID (3 entities in total) |
| Functional Keywords | nucleocapsid protein, nucleoprotein, nucleocapsid, viral protein |
| Biological source | Phlebovirus |
| Total number of polymer chains | 5 |
| Total formula weight | 142933.86 |
| Authors | |
| Primary citation | Jiao, L.,Ouyang, S.,Liang, M.,Niu, F.,Shaw, N.,Wu, W.,Ding, W.,Jin, C.,Peng, Y.,Zhu, Y.,Zhang, F.,Wang, T.,Li, C.,Zuo, X.,Luan, C.H.,Li, D.,Liu, Z.J. Structure of severe Fever with thrombocytopenia syndrome virus nucleocapsid protein in complex with suramin reveals therapeutic potential J.Virol., 87:6829-6839, 2013 Cited by PubMed Abstract: Severe fever with thrombocytopenia syndrome is an emerging infectious disease caused by a novel bunyavirus (SFTSV). Lack of vaccines and inadequate therapeutic treatments have made the spread of the virus a global concern. Viral nucleocapsid protein (N) is essential for its transcription and replication. Here, we present the crystal structures of N from SFTSV and its homologs from Buenaventura (BUE) and Granada (GRA) viruses. The structures reveal that phleboviral N folds into a compact core domain and an extended N-terminal arm that mediates oligomerization, such as tetramer, pentamer, and hexamer of N assemblies. Structural superimposition indicates that phleboviral N adopts a conserved architecture and uses a similar RNA encapsidation strategy as that of RVFV-N. The RNA binding cavity runs along the inner edge of the ring-like assembly. A triple mutant of SFTSV-N, R64D/K67D/K74D, almost lost its ability to bind RNA in vitro, is deficient in its ability to transcribe and replicate. Structural studies of the mutant reveal that both alterations in quaternary assembly and the charge distribution contribute to the loss of RNA binding. In the screening of inhibitors Suramin was identified to bind phleboviral N specifically. The complex crystal structure of SFTSV-N with Suramin was refined to a 2.30-Å resolution. Suramin was found sitting in the putative RNA binding cavity of SFTSV-N. The inhibitory effect of Suramin on SFTSV replication was confirmed in Vero cells. Therefore, a common Suramin-based therapeutic approach targeting SFTSV-N and its homologs could be developed for containing phleboviral outbreaks. PubMed: 23576501DOI: 10.1128/JVI.00672-13 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.303 Å) |
Structure validation
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