Abstract
Cooperative behavior in the binding of ligands to a protein is often viewed as a complex phenomenon where conformational changes induced by the binding of the first ligand leads to tighter binding of subsequent ligands. We revisit the ligand-dependent activation of dimeric transcription factors and show that this process may appear cooperative even when it results from independent ligand binding events. This effect is further accentuated through binding of the activated transcription factor to its cognate operator site on the DNA, where we demonstrate that cooperative activation is a stable fixed point. Our analysis nicely accounts for the apparent co-operativity inherent in the biological activity of many dimeric transcription factors.
Highlights
The central dogma of biology describes how genetic information flows from DNA to RNA and thence to protein [1]
This effect is further accentuated through binding of the activated transcription factor to its cognate operator site on the DNA, where we demonstrate that cooperative activation is a stable fixed point
Our analysis accounts for the inherent cooperativity in the biological activity of many dimeric transcription factors
Summary
The central dogma of biology describes how genetic information flows from DNA to RNA and thence to protein [1]. Transcription factors are capable of recognizing discrete DNA sequence motifs in regulatory regions called operators located just upstream of the gene(s) of interest. Once bound to these operator regions, the transcription factor either recruits (if it is acting to stimulate expression of the gene) or blocks (if it is acting to repress expression of the gene) access of the RNA-synthesizing enzyme, RNA polymerase, to its binding site on the DNA. The binding site of RNA polymerase on a gene is known as the promoter and this is usually closely juxtaposed with the operator This way, binding of a transcription factor to an operator site can alter the transcription rate of the associated gene. If the gene encodes a protein, the elevated rate of transcription yields more messenger RNA, which in turn yields proportionally more protein following translation
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