PMID- 31021526
OWN - NLM
STAT- MEDLINE
DCOM- 20200225
LR  - 20200309
IS  - 2211-5463 (Electronic)
IS  - 2211-5463 (Linking)
VI  - 9
IP  - 6
DP  - 2019 Jun
TI  - Structural insights into interactions between viral suppressor of RNA silencing 
      protein p19 mutants and small RNAs.
PG  - 1042-1051
LID - 10.1002/2211-5463.12644 [doi]
AB  - Viral suppressors of RNA silencing (VSRSs) are a diverse group of viral proteins 
      that have evolved to disrupt eukaryotic RNA silencing pathways, thereby 
      contributing to viral pathogenicity. The p19 protein is a VSRS that selectively 
      binds to short interfering RNAs (siRNAs) over microRNAs (miRNAs). Mutational 
      analysis has identified single amino acid substitutions that reverse this 
      selectivity through new high-affinity interactions with human miR-122. Herein, we 
      report crystal structures of complexed p19-T111S (2.6 A), p19-T111H (2.3 A) and 
      wild-type p19 protein (2.2 A) from the Carnation Italian ringspot virus with 
      small interfering RNA (siRNA) ligands. Structural comparisons reveal that these 
      mutations do not lead to major changes in p19 architecture, but instead promote 
      subtle rearrangement of residues and solvent molecules along the p19 midline. 
      These observations suggest p19 uses many small interactions to distinguish siRNAs 
      from miRNAs and perturbing these interactions can create p19 variants with novel 
      RNA-recognition properties. DATABASE: Model data are deposited in the PDB 
      database under the accession numbers 6BJG, 6BJH and 6BJV.
CI  - (c) 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
FAU - Foss, Dana V
AU  - Foss DV
AD  - Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 
      Canada.
FAU - Schirle, Nicole T
AU  - Schirle NT
AD  - Department of Integrative Structural and Computational Biology, The Scripps 
      Research Institute, La Jolla, CA, USA.
FAU - MacRae, Ian J
AU  - MacRae IJ
AD  - Department of Integrative Structural and Computational Biology, The Scripps 
      Research Institute, La Jolla, CA, USA.
FAU - Pezacki, John Paul
AU  - Pezacki JP
AD  - Department of Chemistry and Biomolecular Sciences, University of Ottawa, Canada.
LA  - eng
GR  - R01 GM104475/GM/NIGMS NIH HHS/United States
GR  - R01 GM115649/GM/NIGMS NIH HHS/United States
GR  - R35 GM127090/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190517
PL  - England
TA  - FEBS Open Bio
JT  - FEBS open bio
JID - 101580716
RN  - 0 (MIRN122 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Mutant Proteins)
RN  - 0 (RNA, Double-Stranded)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Viral Core Proteins)
RN  - Carnation Italian ringspot virus
SB  - IM
MH  - Binding Sites/genetics
MH  - Cells, Cultured
MH  - Crystallization
MH  - Crystallography, X-Ray
MH  - Escherichia coli/cytology
MH  - Humans
MH  - Hydrogen Bonding
MH  - MicroRNAs/chemistry
MH  - Mutant Proteins/*chemistry
MH  - Point Mutation
MH  - Protein Binding
MH  - Protein Engineering/methods
MH  - Protein Structure, Secondary
MH  - *RNA Interference
MH  - RNA, Double-Stranded
MH  - RNA, Small Interfering/*chemistry
MH  - *Tombusvirus
MH  - Viral Core Proteins/*chemistry/genetics
PMC - PMC6551489
OTO - NOTNLM
OT  - X-ray crystallography of protein:RNA complex
OT  - engineering RNA binding proteins
OT  - p19 protein
OT  - protein:RNA interactions
COIS- The authors declare no conflict of interest.
EDAT- 2019/04/26 06:00
MHDA- 2020/02/26 06:00
PMCR- 2019/05/17
CRDT- 2019/04/26 06:00
PHST- 2019/02/19 00:00 [received]
PHST- 2019/04/03 00:00 [revised]
PHST- 2019/04/24 00:00 [accepted]
PHST- 2019/04/26 06:00 [pubmed]
PHST- 2020/02/26 06:00 [medline]
PHST- 2019/04/26 06:00 [entrez]
PHST- 2019/05/17 00:00 [pmc-release]
AID - FEB412644 [pii]
AID - 10.1002/2211-5463.12644 [doi]
PST - ppublish
SO  - FEBS Open Bio. 2019 Jun;9(6):1042-1051. doi: 10.1002/2211-5463.12644. Epub 2019 
      May 17.