Promoter site structure

To influence the activity of RNA polymerase, transcription factors bind to DNA at enhancer sites and/or promoter sites. Four different structures of these factors are known. They possess structures that allow specific binding to DNA. They are given names that indicate the key protein domains that encourage this binding, as follows ... 

It is far from easy to distinguish structural, electronic and synergistic promotion effects. Structural promotion is, in this respect, the most easily to observe. Most synergistic elfects are also widely discussed in the literature in enhancing the catalytic performance of supported cobalt nanoparticles. Instead, promotion as a result of electronic effects are much more difficult to detect. The main reason is that one has to discriminate between the number of surface cobalt sites and the intrinsic activity of a surface cobalt site (turnover frequency). This is especially difficult in view of the complexity of the catalyst material. It also requires spectroscopic tools, which are able to detect changes in the electronic structure of the supported cobalt nanoparticles. 

TFIIA and TFIIB support TFIID in the formation of a stable complex with the promotor. TFllB is necessary for the downstream selection of the start site for RNA polymerase 11. Interactions with TFllB ensure correct positioning of the RNA polymerase 11 on the promoter. Crystal structures have been solved for several of the intermediates of the pre-initiation complex (review Sokolev and Burley, 1997), showing, for example, that TBP affects a predominant kink in the DNA (see Fig. 1.16). TFIIB binds to the TBP-DNA complex, contacting both TBP and the DNA. 

Figure 13.1 Operon model for control of protein synthesis. The example chosen is the lactose (lac) operon. I, regulatory gene p, promoter site o, operator gene z, y, and a represent the structural genes for j8-galactosidase, permease, and transacetylase, respectively.

ALS because SODl encodes for an antioxidant enzyme. Although the relevance of oxidative stress is not fully understood, it is believed that mutations in SODl promote a structural change that allows a higher rate of interaction between the substrates and the active site of the enzyme, resulting in increased production of free radical species. However, there are not sufficient experimental data supporting this hypothesis because if SODl mutants cause peroxynitrite-dependent cell death in vitro, it would be expected that reduction in the levels of peroxynitrite by inhibition of neuronal nitric oxide synthase (nNOS) would improve the motor neuron outcomes. However, these experiments did not show a decrease in motor neuron damage (Facchinetti et ah, 1999 Upton-Rice et ah, 1999 Son et ah, 2001). 

Figure 4 Direct and indirect models of metal ion activation of ribozyme catalysis. Model of classes of metal sites that influence ribozyme activity. The scheme on top depicts the binding of a metal ion important for ribozyme folding that binds distant from the active site but promotes a structural transition that permits catalysis or the binding of catalytic metal ions. Such binding interactions may result directly in overall folding or may merely foster small stmctural changes near the active site that are critical to ribozyme chemistry. The scheme below depicts the direct activation of ribozyme activity by binding of metal ions that interact with the reactive phosphate and are involved in metal ion catalysis. Adapted from Reference 38.

In an inducible system, the repressor protein normally binds to a modulator site called the operator, O, and consequently blocks transcription of the adjacent structural genes. However, when the specific inducer for the system is present in an appropriate environment, inducer binds to the repressor and alters its conformation so that the repressor is released from the operator site. The promoter site is thereby freed, and the transcription machinery can initiate synthesis of mRNA. The mRNA, in turn, is translated to yield the protein products of the operon. In a repressive system, the operon is normally expressed because the repressor protein normally has a conformation that prevents its binding to the operator site. However, when the specific corepressor for the system is present, corepressor binds to the (apojreoressor protein and alters its conformation so that repressor now binds the operator and blocks the initiation of transcription at the promoter site. 

Figure 3. Antiterminator control of transcription termination. A regulatory gene, R, codes for an antiterminator protein. The control region of DNA preceding the structural genes, SG, which in Figures 1 and 2 consisted of modulator and promoter sites, has been expanded and redefined as the leader region, which begins with a promoter, P, and ends with a terminator, T. (For simplicity, initiation of transcription is assumed to occur constitutively at the promoter.)...

---