DNA binding dimers

ERs have domains responsible for nuclear location, hormone binding, dimerization, DNA binding, and transcription activation (Figs. 1.2 and 1.3) (Beato et al. 1996 Beato 1989 Fawell et al. 1990 Hall et al. 1999 Kumar et al. 1987). 

Fig. 1.6. The Zn binding motif of the glncocorticoid receptor in complex with DNA. Shown is the complex of the dimeric DNA-binding domain of the glncocorticoid receptor with the cognate DNA element (Luisi et al., 1991). The Zn ions are shown as spheres. The two Zn ions are clearly non-eqnivalent. While one of the Zn ions aids in the fixation of the recognition helix in the major groove, the other correctly positions a strnctnral element for the dimerization of the monomers. MOLSCRIPT drawing (Kranhs, 1991).

Fig. 4.8. Functional domains, DNA-binding and HRE structure of the steroid hormone receptors. a) domain structure of the steroid hormone receptor. AFl, AF2 domains that mediate the stimulation of the transcription, b) schematic representation of the two Zn -Cys4 binding motils of the DNA-binding domains, c) Complex formation between the dimeric DNA-binding domains of the gluccocorticoid receptor and the HRE. The black spheres represent Zn ions. After Luisi et al., 199L d) Consensus sequence and configuration of the HRE elements of the steroid hormone receptor.

Figure 31.31. Cyclic AMP-Response Element Binding Protein (CREB). Each of two CREB subunits contributes a long a helix. The two helices coil around each other to form a dimeric DNA-binding unit. CREB is phosphorylated on a specific serine residue by protein kinase A.

The inverted repeat may be a binding site for a dimeric DNA-binding protein or it may correspond to a stem-loop structure in the encoded RNA. 

Figure 7.3 Mechanism of action of progesterone, PAs and SPRMs. Binding of progesterone (a) to the inactive receptor complex induces a conformational change, which leads to heat shock protein dissociation, receptor dimerization, DNA binding, and recruitment of coactivators to facilitate communication with the PRE. PAs (a) induce an altered conformation in PR that is...

Jiang BH, Rue E, Wang GL, Roe R, Semenza GL. Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J Biol Chem 1996 271 17771-17778. 

In spite of the absence of the C-terminal domains, the DNA-binding domains of lambda repressor form dimers in the crystals, as a result of interactions between the C-terminal helix number 5 of the two subunits that are somewhat analogous to the interactions of the C-terminal p strand 3 in the Cro protein (Figure 8.7). The two helices pack against each other in the normal way with an inclination of 20° between the helical axes. The structure of the C-terminal domain, which is responsible for the main subunit interactions in the intact repressor, remains unknown. 

Approximately 10 base pairs are required to make one turn in B-DNA. The centers of the palindromic sequences in the DNA-binding regions of the operator are also separated by about 10 base pairs (see Table 8.1). Thus if one of the recognition a helices binds to one of the palindromic DNA sequences, the second recognition a helix of the protein dimer is poised to bind to the second palindromic DNA sequence. 

This model of Cro binding to DNA was arrived at by intuition and clever model building. Its validity was considerably strengthened when the same features were subsequently found in the DNA-binding domains of the lambda-repressor molecule. The helix-turn-helix motif with a recognition helix is present in the repressor, and moreover the repressor DNA-binding domains dimerize in the crystals in such a way that the recognition helices are separated by 34 A as in Cro. 

Figure 8.11 The DNA-binding domain of 434 repressor. It is a dimer in its complexes with DNA fragments. Each subunit (green and brown) folds into a bundle of four a helices (1-4) that have a structure similar to the corresponding region of the lambda repressor (see Figure 8.7) including the helix-turn-helix motif (blue and red). A fifth a helix (5) is involved in the subunit interactions, details of which are different from those of the lambda repressor fragment. The structure of the 434 Cro dimer is very similar to the 434 repressor shown here.

The tetrameric structure of the lac repressor has a quite unusual V-shape (Figure 8.22). Each arm of the V-shaped molecule is a tight dimer, which is very similar in structure to the PurR dimer and which has the two N-termi-nal DNA binding domains close together at the tip of the arm. The two dimers of the lac repressor are held together at the other end by the four carboxy-terminal a helices, which form a four-helix bundle. 

Some of the procaryotic DNA-binding proteins are activated by the binding of an allosteric effector molecule. This event changes the conformation of the dimeric protein, causing the helix-tum-helix motifs to move so that they are 34 A apart and able to bind to the major groove. The dimeric repressor for purine biosynthesis, PurR, induces a sharp bend in DNA upon binding caused by insertion of a helices in the minor groove between the two... 

The homeodomain frequently binds to DNA as a monomer, in contrast to procaryotic DNA-binding proteins containing tbe belix-turn-helix motif, which usually bind as dimers. In vitro tbe homeodomain binds specifically to... 

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