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PDBsum entry 4j4r
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Viral protein
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PDB id
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4j4r
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PDB id:
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| Name: |
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Viral protein
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Title:
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Hexameric sftsvn
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Structure:
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Nucleocapsid protein. Chain: a. Synonym: sftsvn. Engineered: yes
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Source:
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Phlebovirus. Organism_taxid: 1205901. Strain: js2010-018. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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1.90Å
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R-factor:
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0.180
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R-free:
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0.204
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Authors:
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L.Jiao,S.Ouyang,M.Liang,F.Niu,N.Shaw,W.Wu,W.Ding,C.Jin,Y.Zhu,F.Zhang, T.Wang,C.Li,X.Zuo,C.H.Luan,D.Li,Z.J.Liu
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Key ref:
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L.Jiao
et al.
(2013).
Structure of severe fever with thrombocytopenia syndrome virus nucleocapsid protein in complex with suramin reveals therapeutic potential.
J Virol,
87,
6829-6839.
PubMed id:
DOI:
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Date:
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07-Feb-13
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Release date:
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22-May-13
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PROCHECK
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Headers
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References
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I6WJ72
(NCAP_SFTS) -
Nucleoprotein from Dabie bandavirus
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Seq:
Struc:
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245 a.a.
248 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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DOI no:
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J Virol
87:6829-6839
(2013)
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PubMed id:
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Structure of severe fever with thrombocytopenia syndrome virus nucleocapsid protein in complex with suramin reveals therapeutic potential.
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L.Jiao,
S.Ouyang,
M.Liang,
F.Niu,
N.Shaw,
W.Wu,
W.Ding,
C.Jin,
Y.Peng,
Y.Zhu,
F.Zhang,
T.Wang,
C.Li,
X.Zuo,
C.H.Luan,
D.Li,
Z.J.Liu.
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ABSTRACT
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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.
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Links
