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Journal of Virology, May 2008, p. 4656-4659, Vol. 82, No. 9
0022-538X/08/$08.00+0     doi:10.1128/JVI.02077-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Residue L143 of the Foot-and-Mouth Disease Virus Leader Proteinase Is a Determinant of Cleavage Specificity{triangledown}

Christina Mayer,1,{dagger} David Neubauer,1,{dagger} Aloysius T. Nchinda,2 Regina Cencic,1,{ddagger} Katja Trompf,1 and Tim Skern1*

Max F. Perutz Laboratories, Medical University of Vienna, Dr. Bohr-Gasse 9/3, A-1030 Vienna, Austria,1 Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa2

Received 19 September 2007/ Accepted 7 February 2008

The foot-and-mouth disease virus (FMDV) leader proteinase (Lpro) self-processes inefficiently at the Lpro/VP4 cleavage site LysLeuLys*GlyAlaGly (* indicates cleaved peptide bond) when the leucine at position P2 is replaced by phenylalanine. Molecular modeling and energy minimization identified the Lpro residue L143 as being responsible for this discrimination. The variant Lpro L143A self-processed efficiently at the Lpro/VP4 cleavage site containing P2 phenylalanine, whereas the L143M variant did not. Lpro L143A self-processing at the eIF4GII sequence AspPheGly*ArgGlnThr was improved but showed more-extensive aberrant processing. Residue 143 in Lpro is occupied only by leucine and methionine in all sequenced FMDV serotypes, implying that these bulky side chains are one determinant of the restricted specificity of Lpro.

* Corresponding author. Mailing address: Medical University of Vienna, Max F. Perutz Laboratories, Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria. Phone: 43 1 4277 61620. Fax: 43 1 4277 9616. E-mail: timothy.skern{at}meduniwien.ac.at

{triangledown} Published ahead of print on 27 February 2008.

{dagger} These authors contributed equally to this work.

{ddagger} Present address: Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec, Canada H3G 1Y6.

Journal of Virology, May 2008, p. 4656-4659, Vol. 82, No. 9
0022-538X/08/$08.00+0     doi:10.1128/JVI.02077-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • de los Santos, T., Diaz-San Segundo, F., Zhu, J., Koster, M., Dias, C. C. A., Grubman, M. J. (2009). A Conserved Domain in the Leader Proteinase of Foot-and-Mouth Disease Virus Is Required for Proper Subcellular Localization and Function. J. Virol. 83: 1800-1810 [Abstract] [Full Text]  


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