NMR structure of the mengovirus Leader protein zinc-finger domain

Cornilescu, Claudia C.; Porter, Frederick W.; Zhao, Kate Qin; Palmenberg, Ann C.; Markley, John L.

doi:10.1016/j.febslet.2008.02.023

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Volume 582, Issue 6 , Pages 896-900, 19 March 2008

NMR structure of the mengovirus Leader protein zinc-finger domain

Edited by Hans Eklund

Claudia C. Cornilescu
- Department of Biochemistry, University of Wisconsin–Madison, Madison, WI 53706-1544, United States
- Center for Eukaryotic Structural Genomics, University of Wisconsin–Madison, Madison, WI 53706-1544, United States
- Corresponding author. Address: Department of Biochemistry, University of Wisconsin–Madison, Madison, WI 53706-1544, United States. Fax: +1 608 262 3759.
Frederick W. Porter
- Department of Biochemistry, University of Wisconsin–Madison, Madison, WI 53706-1544, United States
- Institute for Molecular Virology, University of Wisconsin-Madison, Madison, WI 53706, United States
Kate Qin Zhao
- Department of Biochemistry, University of Wisconsin–Madison, Madison, WI 53706-1544, United States
- Center for Eukaryotic Structural Genomics, University of Wisconsin–Madison, Madison, WI 53706-1544, United States
- Present address: Promega Corporation, 2800 Woods Hollow Road, Madison, WI 53711, United States.
Ann C. Palmenberg
- Department of Biochemistry, University of Wisconsin–Madison, Madison, WI 53706-1544, United States
- Institute for Molecular Virology, University of Wisconsin-Madison, Madison, WI 53706, United States
John L. Markley
- Department of Biochemistry, University of Wisconsin–Madison, Madison, WI 53706-1544, United States
- Center for Eukaryotic Structural Genomics, University of Wisconsin–Madison, Madison, WI 53706-1544, United States

Received 11 October 2007; received in revised form 6 February 2008; accepted 6 February 2008. published online 19 February 2008.

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.

Abbreviations: EMCV, encephalomyocarditis virus, GDP, guanosine diphosphate, GST, glutathione S-transferase, GTP, guanosine triphosphate, L, Leader protein, L_M, 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’s murine encephalomyocarditis virus