Sequence-specific interactions with DNA

Figure 10.4 Detailed view of the binding of the second zinc finger of Zif 268 to DNA. Two side chains, Arg 46 and His 49, form sequence-specific interactions with DNA. There are also three nonspecific interactions between phosphate groups of the DNA and the side chains of Arg 42, Ser 45, and His 53.

Three residues in the recognition helix provide the sequence-specific interactions with DNA... 

DNA has a MAJOR AND MINOR GROOVE because the bases attach at an angle that is not 180° apart around the axis of the helix. The major groove has more of the bases exposed. Sequence-specific interactions with DNA often occur along the major groove. Since the helix is right-handed, the next ribose shown... 

Strand invasion, an alternative approach to obstructing transcription by formation of triple strands, has been shown to be feasible if analogs with sufficient affinity can be synthesized. PNAs have been shown to have very hyi affinity and be capable of strand invasion of double-stranded DNA under some conditions (51). Additionally, progress in develop-irg sequence-specific minor groove binders has been reported (52) (for review, see Ref 53). Thus, progress in developing the basic tools with which to evaluate the potential of sequence-specific interactions with DNA has bcai reported, although much remains to be dene. 

Figure 9.10 Schematic diagrams illustrating the complex between DNA (orange) and one monomer of the homeodomain. The recognition helix (red) binds in the major groove of DNA and provides the sequence-specific interactions with bases in the DNA. The N-terminus (green) binds in the minor groove on the opposite side of the DNA molecule and arginine side chains make nonspecific interactions with the phosphate groups of the DNA. (Adapted from C.R. Kissinger et al Cell 63 579-590, 1990.)...

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). 

Figure 9.20 Diagram iliustrating the sequence-specific interactions between DNA and p53. The C-terminai a helix and loop LI of p53 bind in the major groove of the DNA. Arg 280 from the a helix and Lys 120 from LI form important specific interactions with bases of the DNA. In addition, Arg 248 from loop L3 binds to the DNA in the minor groove. (Adapted from Y. Cho et al.. Science 265 346-355, 1994.)...

Figure 10.11 Sequence-specific interactions between DNA (yellow) and the recognition helix (red) of the glucocorticoid receptor. Three residues, Lys 461, Val 462 and Arg 466 make specific contacts with the edges of the bases In the major groove.

There is only one sequence-specific interaction with an amino acid side chain, which is provided by Lys 18 (red). The linker region is an extended chain that follows one strand of the DNA and provides several nonspecific contacts (blue) to the DNA. The numbering of the base pairs starts from the center of the DNA fragment. (Adapted from R. Matmorstein et al., Nature 356 408 14, 1992.)... 

Three residues. His 28, Glu 32 and Arg 36, form specific interactions with the edges of the bases in the major groove of DNA. Like MyoD, a Glu residue recognizes the first two bases, C and A, of the recognition sequence. 

Fig. 1.6. Binding domain to DNA. ERs contain two structures called zinc fingers, typical of proteins that interact with DNA. One zinc atom forms four links of coordination with four cysteine residues of the protein structure, which occupy nearby positions, thus leaving a loop of some 15 to 22 aminoacids. The zinc fingers of the receptor are capable of interacting with specific sequences of DNA, the hormone response elements, with which they establish hydrogen bridges and form stable structures...

Dempsey LA, Hanakahi LA, Maizels N (1998) A specific isoform of hnRNP D interacts with DNA in the LRl heterodimer canonical RNA binding motifs in a sequence-specific duplex DNA binding protein. J Biol Chem 273 29224-29229... 

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