In the other DNA-binding motifs displayed in this panel, ˜ helices are the primary mechanism used to recognize specifc DNA sequences. In one large group of transcription regulators, however, a two-stranded ° sheet, with amino acid side chains extending from the sheet toward the DNA, reads the information on the surface of the major groove. As in the case of a recognition ˜ helix, this °-sheet motif can be used to recognize many different DNA sequences; the exact DNA sequence recognized depends on the sequence of amino acids that make up the ° sheet. Shown is a transcription regulator that binds two molecules of S-adenosyl methionine (red). On the left is a dimer of the protein; on the right is a simplifed diagram showing just the two-stranded ° sheet bound to the major groove of DNA. This group of DNA-binding motifs includes one or more zinc atoms as structural components. All such zinc-coordinated DNA-binding motifs are called zinc fngers, referring to their appearance in early schematic drawings (left). They fall into several distinct structural groups, only one of which we consider here. It has a simple structure, in which the zinc atom holds an ˜ helix and a ° sheet together (middle). This type of zinc fnger is often found in clusters with the ˜ helix of each fnger contacting the major groove of the DNA, forming a nearly continuous stretch of ˜ helices along that groove. In this way, a strong and specifc DNA–protein interaction is built up through a repeating basic structural unit. Three such fngers are shown on the right.N C C N C His Cys Zn His N Cys CCGLEHHZnKYKNQRVRRSFKEVLSASCOOHNH2COOHNH2ZnZnZnDNADNA° SHEET DNA RECOGNITION PROTEINS ZINC FINGER PROTEINS 377
Related to the leucine zipper, the helix–loop–helix motif consists of a short ˜ helix connected by a loop (red) to a second, longer ˜ helix. The fexibility of the loop allows one helix to fold back and park against the other thereby forming the dimerization surface. As shown, this two-helix structure binds both to DNA and to the two-helix structure of a second protein to create either a homodimer or a heterodimer. Two ˜helices that extend from the dimerization interface make specifc contacts with the major groove of DNA. CCNNDNAloopHELIX–LOOP–HELIX PROTEINS recognized by the protein has increased from approximately 6 nucleotide pairs to 12 nucleotide pairs, there are many fewer random occurrences of matching sequences.
Heterodimers are often formed from two different transcription regulators. Transcription regulators may form heterodimers with more than one partner protein; in this way, the same transcription regulator can be “reused” to create several distinct DNA-binding specificities (see Figure 7–9C).
transcription regulators Bind Cooperatively to DnA
In the simplest case, the collection of noncovalent bonds that holds the above dimers or heterodimers together is so extensive that these structures form obligatorily, and never fall apart. In this case, the unit of binding is the dimer or heterodimer, and the binding curve for the transcription regulator (the fraction of DNA bound as a function of protein concentration) has a standard exponential shape (Figure 7–10A).
In many cases, however, the dimers and heterodimers are held together very weakly; they exist predominantly as monomers in solution, and yet dimers are observed on the appropriate DNA sequence. Here, the proteins are said to bind to DNA cooperatively, and the curve describing their binding is sigmoidal in shape (Figure 7–10B). Cooperative binding means that, over a range of concentrations of the transcription regulator, binding is more of an all-or-none phenomenon than