The RNA-Binding Site of Poliovirus 3C Protein Doubles as a Phosphoinositide-Binding Domain

Djoshkun Shengjuler, Yan Mei Chan, Simou Sun, Ibrahim M. Moustafa, Zhen Lu Li, David W. Gohara, Matthias Buck, Paul S. Cremer, David D. Boehr, Craig E. Cameron

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Some viruses use phosphatidylinositol phosphate (PIP) to mark membranes used for genome replication or virion assembly. PIP-binding motifs of cellular proteins do not exist in viral proteins. Molecular-docking simulations revealed a putative site of PIP binding to poliovirus (PV) 3C protein that was validated using nuclear magnetic resonance spectroscopy. The PIP-binding site was located on a highly dynamic α helix, which also functions in RNA binding. Broad PIP-binding activity was observed in solution using a fluorescence polarization assay or in the context of a lipid bilayer using an on-chip, fluorescence assay. All-atom molecular dynamics simulations of the 3C protein-membrane interface revealed PIP clustering and perhaps PIP-dependent conformations. PIP clustering was mediated by interaction with residues that interact with the RNA phosphodiester backbone. We conclude that 3C binding to membranes will be determined by PIP abundance. We suggest that the duality of function observed for 3C may extend to RNA-binding proteins of other viruses. The absence of conventional PIP-binding domains in viral proteins suggests unique structural solutions to this problem. Shengjuler et al. show that a viral RNA-binding site can be repurposed for PIP binding. PIP clustering can be achieved. The nature of the PIP may regulate protein conformation.

Original languageEnglish (US)
Pages (from-to)1875-1886.e7
Issue number12
StatePublished - Dec 5 2017

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology


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