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NMR structure of the mengovirus Leader protein zinc-finger domain
Authors:Cornilescu Claudia C  Porter Frederick W  Zhao Kate Qin  Palmenberg Ann C  Markley John L
Affiliation:a Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706-1544, United States
b Center for Eukaryotic Structural Genomics, University of Wisconsin-Madison, Madison, WI 53706-1544, United States
c Institute for Molecular Virology, University of Wisconsin-Madison, Madison, WI 53706, United States
Abstract:The Leader protein is a defining feature of picornaviruses from the Cardiovirus genus. This protein was recently shown to inhibit cellular nucleocytoplasmic transport through an activity mapped to its zinc-binding region. Here we report the three-dimensional solution structure determined by nuclear magnetic resonance (NMR) spectroscopy of this domain (residues 5-28) from mengovirus. The domain forms a CHCC zinc-finger with a fold comprising a β-hairpin followed by a short α-helix that can adopt two different conformations. This structure is divergent from those of other eukaryotic zinc-fingers and instead resembles motifs found in a group of DNA-binding proteins from Archaea.
Keywords:EMCV, encephalomyocarditis virus   GDP, guanosine diphosphate   GST, glutathione S-transferase   GTP, guanosine triphosphate   L, Leader protein   LM, Leader protein from Mengovirus   MALDI-MS, matrix assisted laser desorption ionization- mass spectrometry   NLS, nuclear localization signal   NMR, nuclear magnetic resonance   rmsd, root mean square deviation   SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis   TMEV, Theiler&rsquo  s murine encephalomyocarditis virus
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