Dimerization regions

Figure 10.25 Structure of the dimerization region of MyoD. The a helices HI (red and brown) and H2 (light and dark green) of the two monomers form a four-helix bundle that keeps the dimer together. The loops (yellow and orange) are on the outside of the four-helix bundle. (Adapted from P.C.M. Ma et al.. Cell 77 4S1-4S9, 1994.)...

Dimerization of the Ce-zinc cluster transcription factors involves an a-helical coiled coil in the dimerization region. Coiled coils, often called leucine zippers, are also found in a large group of transcription factors that do not contain zinc. The leucine zipper is made up of two a helices in a coiled coil with every seventh residue leucine or some other large hydrophobic residue, such as isoleucine or valine. Leucine zipper transcription factors (b/zip) include factors characterized by heterodimerization, for example Fos and Jun. The a-helical DNA-binding motifs of the heterodimers recognize quite different base sequences and are continous with the a helices of the zipper. 

Helix-loop-helix (b/HLH) transcription factors are either heterodimers or homodimers with basic a-helical DNA-binding regions that lie across the major groove, rather than along it, and these helices extend into the four-helix bundle that forms the dimerization region. A modification of the b/HLH structure is seen in some transcription factors (b/HLH/zip) in which the four-helix bundle extends into a classic leucine zipper. 

At least three regions of the receptor participate in the process of dimer formation. One of them is unspecific and is made up of the sequences of hydrophobic amino acids of the LBD. These form hydrophobic contact surfaces that facilitate, in a general way, the interactions among proteins. The other two are specific sequences of amino acids. One of them is situated immediately after the DBD. It is comprised of a group of some 20 amino acids, and its capacity to intervene in the dimer is independent of binding to the hormone. The other dimerization region is found inside the LBD. It is poorly located, and it is possible that noncontiguous sequences of amino acids participate in it. It is exhibited only when the receptor has been already bound to a hormone. 

The helix-loop-helix motif appears to be another way of creating heterodimers that can bind to asymmetric sites on the DNA. Like the leucine zipper proteins, the helix-loop-helix proteins have a basic region that contacts the DNA and a neighboring region that mediates dimer formation. Based on sequence patterns, it has been proposed that this dimerization region forms an a helix, a loop, and a second a helix. Like the leucine zipper protein, the activity of the helix-loop-helix proteins is modulated by heterodimer formation. For example, the MyoD protein, which appears to be the primary signal for differentiation of muscle cells, binds DNA most tightly when it forms a heterodimer with the ubiquitously expressed E2A protein. 

Nilges, M., and Brunger, A. T. (1991). Automated modeling of coiled coils Application to the GCN4 dimerization region. Protein Eng. 4, 649-659. 

Helix-loop-helix transcription factors are a fourth stractural type of DNA binding protein (see Fig. 16.16D). They also function as dimers that fit around and grip DNA in a manner geometrically similar to leucine zipper proteins. The dimerization region consists of a portion of the DNA-gripping helix and a loop to another helix. Like leucine zippers, helix-loop-helix factors can function as either hetero or homodimers. These factors also contain regions of basic amino acids near the amino terminus and are also called basic helix-loop-helix (bHLH) proteins. 

I— Monomer region — >- Dimer region —I I- Trimer region -I... 

As a result of the degenerate ground state, an immediate and fascinating consequence of bond-alternation are bond-defects, or solitons. Solitons separate a dimerized region A from a dimerized region B, and thus they resemble domain walls in ferromagnets. 

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