DNA-complexes

Mineralocorticoids foUow a mechanistic route similar to that of glucocorticoids, though differing in the proteins expressed. The activated MR-DNA complex promotes the expression of aldosterone-induced proteins (AIPs), which then act to increase conductance of the luminal membrane and concurrently increase pump activity of the basolateral membrane. These actions result from a number of AlP-influenced cellular characteristics,... 

Fig. 2. Two views of the stmcture of the TATA-box binding protein (TBP)—DNA complex, where TATA is the nucleotide sequence...

Protein-DNA complexes present demanding challenges to computational biophysics The delicate balance of forces within and between the protein, DNA, and solvent has to be faithfully reproduced by the force field, and the systems are generally very large owing to the use of explicit solvation, which so far seems to be necessary for detailed simulations. Simulations of such systems, however, are feasible on a nanosecond time scale and yield structural, dynamic, and thermodynamic results that agree well with available experimen-... 

The x-ray structure of DNA complexes with 434 Cro and repressor revealed novel features of protein-DNA interactions... 

Structural studies of a repressor-DNA complex have shown that helices 4 and 5 form a helix-turn-helix motif and that side chains from the recognition helix 5 form water-mediated interactions with bases in the major groove. 

The lac repressor monomer, a chain of 360 amino acids, associates into a functionally active homotetramer. It is the classic member of a large family of bacterial repressors with homologous amino acid sequences. PurR, which functions as the master regulator of purine biosynthesis, is another member of this family. In contrast to the lac repressor, the functional state of PurR is a dimer. The crystal structures of these two members of the Lac I family, in their complexes with DNA fragments, are known. The structure of the tetrameric lac repressor-DNA complex was determined by the group of Mitchell Lewis, University of Pennsylvania, Philadelphia, and the dimeric PurR-DNA complex by the group of Richard Brennan, Oregon Health Sciences University, Portland. 

Many biochemical and biophysical studies of CAP-DNA complexes in solution have demonstrated that CAP induces a sharp bend in DNA upon binding. This was confirmed when the group of Thomas Steitz at Yale University determined the crystal structure of cyclic AMP-DNA complex to 3 A resolution. The CAP molecule comprises two identical polypeptide chains of 209 amino acid residues (Figure 8.24). Each chain is folded into two domains that have separate functions (Figure 8.24b). The larger N-terminal domain binds the allosteric effector molecule, cyclic AMP, and provides all the subunit interactions that form the dimer. The C-terminal domain contains the helix-tum-helix motif that binds DNA. 

Figure 9.12 Schematic diagram of the structure of the heterodimeric yeast transcription factor Mat a2-Mat al bound to DNA. Both Mat o2 and Mat al are homeodomains containing the helix-turn-helix motif. The first helix in this motif is colored blue and the second, the recognition helix, is red. (a) The assumed structure of the Mat al homeodomain in the absence of DNA, based on Its sequence similarity to other homeodomains of known structure, (b) The structure of the Mat o2 homeodomain. The C-terminal tail (dotted) is flexible in the monomer and has no defined structure, (c) The structure of the Mat a 1-Mat a2-DNA complex. The C-terminal domain of Mat a2 (yellow) folds into an a helix (4) in the complex and interacts with the first two helices of Mat a2, to form a heterodimer that binds to DNA. (Adapted from B.J. Andrews and M.S. Donoviel, Science 270 251-253, 1995.)...

Figure 9.19 shows the sequence of the DNA that was used for the structure determination of the p53-DNA complex the bases involved in sequence-specific binding to the protein are shaded. One molecule of the DNA-bind-ing domain of p53 binds to the minor and the major grooves of the DNA making sequence-specific interactions with both strands (Figure 9.20). 

Billeter, M., et al. Determination of the nuclear magnetic resonance solution structure of an Antennapedia home-odomain DNA complex. /. Mol. Biol. 234 1084-1097, 1993. 

Cho, Y., et al. Crystal structure of a p53 tumor suppres-sor DNA complex understanding tumorigenic mutations. Science 265 346-355, 1994. 

Kissinger, C.R., et al. Crystal structure of an engrailed homeodomain DNA complex at 2.8 A resolution a framework for understanding homeodomain-DNA interactions. Cell 63 579-590, 1990. 

Figure 10.6 One sequence-specific interaction occurs more frequently than others in protein-DNA complexes two hydrogen bonds form between an arginine side chain of the protein and a guanine base of the DNA, as shown in this diagram.

Subsequently Stephen Harrison s group determined the x-ray structure of a PPRl-DNA complex and showed that the zinc cluster domain of PPRl and its mode of binding to DNA was very similar to that of GAL4, and that PPRl also dimerized through a coiled-coil region. However, the linker region... 

Ellenberger, T.E., et al. The GCN4 basic region leucine zipper binds DNA as a dimer of uninterrupted a helices crystal structure of the protein-DNA complex. Cell 71 1223-1237, 1992. 

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