Recognition sequence Direct

Harrington, R.E. and Winicov, I. New concepts in protein-DNA recognition sequence directed DNA bending and flexibility (1994) Progr. Nucl. Add Res. Mol. Biol. 47,195-270... 

McDonnell, A. V., Menke, M., Palmer, N., King, J., Cowen, L., and Berger, B. (2006). Fold recognition and accurate sequence-structure alignment of sequences directing beta-sheet proteins. Proteins 63, 976-985. 

The contact between protein and DNA can also be transmitted via boimd water molecules. In the crystal structure of the complex of the bacterial Trp-repressor and the cognate operator sequence are foimd only a few direct H-bonds between the amino acid residues of the protein and the bases of the recognition sequence. Rather, the contacts between protein and nucleic acid are frequently established indirectly by a chain of well-defined bound water molecules which contact the protein and the bases, and thereby function as transmitter between the protein and DNA. 

The recognition sequences for specific DNA-binding proteins usually include only 3-8 base pairs, arranged either palindromically or in direct repeats (Fig. 1.18). The symmetry of the sequence in the DNA element is often reflected in the subunit structure of the binding protein. Less common is the occurrence of a singular recognition sequence. 

Direct repeat of the recognition sequence requires a nonsymmetrical spatial arrangement of the bound protein subunits (see chapter 4, Nuclear Receptors). The protein-DNA complex has, in this case, a polar character and the protein bound on each of the two halves of the recognition element can carry out different functions. Direct 2-fold repeats are commonly observed for the DNA-binding elements of the steroid hormone receptors (see chapter 4). 

The DNA binding element of the nuclear receptors for all-trans retinoic acid, for 9-cis retinoic acid, for the T3 hormone and for the vitamin D3 hormone usually exhibit a direct repeat of the recognition sequence, resulting in formation of heterodimers on the DNA (fig. 4.7b). One of the partners in the heterodimer is always the receptor for 9-cis retinoic acid, RXR, and which usually occupies the 5 side of the HRE. 

Of particular importance for receptor binding on HREs with direct repeats of the recognition sequence is the fact that the hexamers of these HREs are arranged head to tail and thus require a polar arrangement of the receptor dimers. 

The orphan receptors" derive their name from the fact that the cognate hormones for these receptors were originally imknown or little understood. Orphan receptors bind as homodimers to recognition sequences arranged as direct repeats (fig. 4.7c). The receptor for 9-cis vitA acid, which also binds as a homodimer an HRE with two halfsites in direct repeats, is also considered a member of this class of receptors. 

Distribution of proteins to tissues is controlled by the permeability (porosity) of the vasculatures and thereby influenced by the molecular size of the protein. A protein of greater than 150kDa ( 50nm) in size will have limited distribution and may be restricted to blood volume. Infrequently a large protein has amino acid recognition sequences that allow passage across epithelial cells lining the vasculatures by transcy-tosis, a process that allows directional transport of protein into and out of a cell. 

K, O2, and C02 (Figure 6.6)., The carboxylation of glutamic acid residues of these proteins appears to be directed by a specific recognition sequence, which is often found in the propeptide to insure binding to the vitamin K-dependent carboxylase. Furie et al., (1999) identified five requirements for gamma carboxylation ... 

A couple of important points exist about the consensus. First, not all bases in the consensus are conserved to the same amount. The bases marked with bold type and underlined are more conserved than the others, and the -10 region is more conserved overall than is the -35 region. Secondly, the promoter sequence is asymmetrical that is, it reads differently in one direction than in the other. (Compare this to the recognition sequence for the restriction enzyme BamHI, GGATCC.) This asymmetry means that RNA polymerase gets directional information from the promoter in addition to information about the starting point for transcription. 

Rarely, the nucleotide sequence change responsible for a disease mutation alters the recognition sequence for a restriction enzyme, enabling the disease gene to be detected simply by the creation or abolition of a restriction endonuclease site. The classic example of direct detection is sickle cell anemia (Fig. 5) an A to T... 

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