Targeting mammalian and vertebrate gene regulatory sequences with a yeast bZIP protein

ORGN 636

I-San Chan, isan_chan@hotmail.com, Anna V. Fedorova, afedorov@utm.utoronto.ca, and Jumi A. Shin, jshin@utm.utoronto.ca. Department of Chemistry, University of Toronto, 3359 Mississauga Road, Mississauga, ON L5L1C6, Canada
The basic region/leucine zipper (bZIP) is the simplest protein structure for targeting specific DNA sequences. We have found a minimalist bZIP protein based on yeast GCN4 that can not only recognize its native sequence, but can also target mammalian and vertebrate gene-regulatory sequences naturally bound by basic region/helix-loop-helix (bHLH) proteins. In addition, the DNA-bZIP protein interaction does not always follow the same mechanism as binding to native yeast sequences. This extended use of the bZIP structure may provide a new design strategy for protein-based drugs, especially for designing transcription factors to manipulate cellular functions.