ORGN 391 |
| We hypothesize that we can exploit what Nature has already evolved by manipulating the ?-helix molecular recognition scaffold. We have designed fusion hybrids comprising the basic region/leucine zipper (bZIP) and basic helix-loop-helix (bHLH) motifs: the DNA-binding basic regions from the bHLH have been fused to the leucine zipper dimerization domains from the bZIP. These hybrids are, therefore, bZIP-like in structure, i.e. a pair of ?-helices, dimerized via the leucine zipper coiled coil, that binds specific DNA sequences via the basic regions. We used the basic regions from bHLH proteins Max, AhR, Arnt, and bZIP protein C/EBP, and leucine zippers from bZIP proteins Jun and Fos. Therefore, these proteins can exist as Jun-Fos heterodimers or Jun-Jun homodimers. To our knowledge, this is the first demonstration of hybrids between different protein families that retain structure and DNA-binding function. With these mutant proteins, we expand the DNA-binding repertoire of the bZIP scaffold. |
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Proteins, Peptides, Amino Acids, and Enzymes
8:00 AM-11:40 AM, Tuesday, 15 March 2005 Convention Center -- Room 9, Oral
Division of Organic Chemistry |