(1) Center for Biological Sequence Analysis, Technical University
of Denmark.
(2) Institute of Biochemistry, University of Vienna, Austria
Picornaviral proteinases are responsible for maturation cleavages of the viral polyprotein but catalyze also the degradation of cellular targets. Using graphical visualization techniques and neural network algorithms we have investigated the sequence specificity of the two proteinases 2Apro and 3Cpro (1). The cleavage of VP0 which is carried out by a so far unknown proteinase was also examined. In combination with a novel surface exposure prediction algorithm our neural network approach successfully distinguishes known cleavage sites from non-cleavage sites and yields a more consistent definition of features common to these sites. The method is able to predict experimentally determined cleavage sites in cellular proteins. We present a list of mammalian and other proteins which are predicted to be possible targets for the viral proteinases. Whether these proteins are indeed cleaved awaits experimental verification. As a side effect, we report several errors detected in the protein databases.
A computer server for prediction of cleavage sites by picornaviral proteinases is made publicly available at the e-mail address NetPicoRNA@cbs.dtu.dk or via WWW at http://www.cbs.dtu.dk/services/NetPicoRNA/
Reference:
(1) Nikolaj Blom, Jan Hansen, Dieter Blaas, and Soren Brunak (1996).
Protein Science, in press.