Basic-region leucine zipper motif

Activation transcription factor-2 (ATF-2 also known as [cAMP-response element (CRE) BP-1] is a member of the ATF/CRE-binding (CREB) family of transcription factors and has a basic region leucine zipper motif (bZip domain) (22,23). This motif is necessary for the formation of heterodimers with other members of the ATF family, as well as with members of tiie Jun/Fos family of factors. The motif is also required for the binding of homodimers of ATF-2 to DRE. ATF-2 and p300 interact with each other in the DRF complex and cooperate in the control of transcription in response to differentiation-inducing signals, such as RA or ElA. 

Gommon motifs are the helix-tum—heUx, zinc fingers, and basic-region leucine zippers. 

The coiled-coil structure of the leucine zipper motif is not the only way that homodimers and heterodimers of transcription factors are formed. As we saw in Chapter 3 when discussing the RNA-binding protein ROP, the formation of a four-helix bundle structure is also a way to achieve dimerization, and the helix-loop-helix (HLH) family of transcription factors dimerize in this manner. In these proteins, the helix-loop-helix region is preceded by a sequence of basic amino acids that provide the DNA-binding site (Figure 10.23), and... 

An important clue to c-myc function was the discovery in the conserved carboxy-terminal regions of three structural motifs, the leucine zipper (LZ), helix-loop-helix (HLH) and basic region (B). These motifs were originally defined in a number of other sequence-specific DNA-bind-ing proteins but had not previously been found within a single protein. 

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. 

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