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Temperature-sensitive protein-DNA dimerizers.

Authors :
Hauschild KE
Metzler RE
Arndt HD
Moretti R
Raffaelle M
Dervan PB
Ansari AZ
Source :
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2005 Apr 05; Vol. 102 (14), pp. 5008-13. Date of Electronic Publication: 2005 Mar 21.
Publication Year :
2005

Abstract

Programmable DNA-binding polyamides coupled to short peptides have led to the creation of synthetic artificial transcription factors. A hairpin polyamide-YPWM tetrapeptide conjugate facilitates the binding of a natural transcription factor Exd to an adjacent DNA site. Such small molecules function as protein-DNA dimerizers that stabilize complexes at composite DNA binding sites. Here we investigate the role of the linker that connects the polyamide to the peptide. We find that a substantial degree of variability in the linker length is tolerated at lower temperatures. At physiological temperatures, the longest linker tested confers a "switch"-like property on the protein-DNA dimerizer, in that it abolishes the ability of the YPWM moiety to recruit the natural transcription factor to DNA. These observations provide design principles for future artificial transcription factors that can be externally regulated and can function in concert with the cellular regulatory circuitry.

Details

Language :
English
ISSN :
0027-8424
Volume :
102
Issue :
14
Database :
MEDLINE
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
15781856
Full Text :
https://doi.org/10.1073/pnas.0501289102