Recognition a helix

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. 

Fig. 5. Protein folding. The unfolded polypeptide chain coUapses and assembles to form simple stmctural motifs such as -sheets and a-hehces by nucleation-condensation mechanisms involving the formation of hydrogen bonds and van der Waal s interactions. Small proteins (eg, chymotrypsin inhibitor 2) attain their final (tertiary) stmcture in this way. Larger proteins and multiple protein assembhes aggregate by recognition and docking of multiple domains (eg, -barrels, a-helix bundles), often displaying positive cooperativity. Many noncovalent interactions, including hydrogen bonding, van der Waal s and electrostatic interactions, and the hydrophobic effect are exploited to create the final, compact protein assembly. Further stmctural...

The protein dimer binds so that the recognition a helices at opposite ends of the protein molecule are in the major groove of the DNA as predicted, where they interact with base pairs at the end of the DNA molecule. Since these binding sites are separated by one turn of the DNA helix, it follows that at the center of the DNA molecule the narrow groove faces the protein... 

Structural studies of a repressor-DNA complex have shown that helices 4 and 5 form a helix-turn-helix motif and that side chains from the recognition helix 5 form water-mediated interactions with bases in the major groove. 

Most sequence-specific regulatory proteins bind to their DNA targets by presenting an a helix or a pair of antiparallel p strands to the major groove of DNA. Recognition of the TATA box by TBP is therefore exceptional it utilizes a concave pleated sheet protein surface that interacts with the minor groove of DNA. Since the minor groove has very few sequence-specific... 

Figure 9.12 Schematic diagram of the structure of the heterodimeric yeast transcription factor Mat a2-Mat al bound to DNA. Both Mat o2 and Mat al are homeodomains containing the helix-turn-helix motif. The first helix in this motif is colored blue and the second, the recognition helix, is red. (a) The assumed structure of the Mat al homeodomain in the absence of DNA, based on Its sequence similarity to other homeodomains of known structure, (b) The structure of the Mat o2 homeodomain. The C-terminal tail (dotted) is flexible in the monomer and has no defined structure, (c) The structure of the Mat a 1-Mat a2-DNA complex. The C-terminal domain of Mat a2 (yellow) folds into an a helix (4) in the complex and interacts with the first two helices of Mat a2, to form a heterodimer that binds to DNA. (Adapted from B.J. Andrews and M.S. Donoviel, Science 270 251-253, 1995.)...

Figure 9.14 The two domains of the POU region bind in tandem on opposite sides of the DNA double helix. Both the POU-specific domain and the POU homeodomain have a helix-turn-helix motif (blue and red) which binds to DNA with their recognition helices (red) in the major groove. The linker region that joins these domains is partly disordered. (Adapted from J.D. Klemm et al.. Cell 77 21-32, 1994.)...

The GAL4 recognition module therefore contains only one protein side chain, Lys 18, that provides specific interactions with the DNA. The remaining specific interactions with DNA are from main-chain atoms and depend critically on the correct conformation of the protein. The correct positioning of the C-terminus of the a helix is particularly important for recognition. This is to date the only example of a protein-DNA interaction in which... 

The crystal structures of DtxR and IdeR provide a detailed picture of this protein family (Figure 3.7, Plate 5). The N-terminal domain (residues 1-73) containing a helix-turn-helix motif binds a recognition nucleotide sequence of about 21 base pairs, as is nicely shown in a cocrystal of DNA and DtxR (Pohl et al., 1999). The central domain (74-140) has a function in dimerization the role of the third carboxy-terminal domain (141-230) is uncertain. Although metal-binding sites have been defined in these crystal structures, the mechanism by which metal binding causes the structural changes between apo- and holo-repressor is not clear. 

IkSnin, I. Pohorille, A. Chipot, C., Insights into the recognition and association of transmembrane a-helices. The free energy of a-helix dimerization in glycophorin A., J. Am. Chem. Soc. 2005,127, 8478-8484... 

Noncovalent interactions play a key role in biodisciplines. A celebrated example is the secondary structure of proteins. The 20 natural amino acids are each characterized by different structures with more or less acidic or basic, hydrophilic or hydrophobic functionalities and thus capable of different intermolecular interactions. Due to the formation of hydrogen bonds between nearby C=0 and N-H groups, protein polypeptide backbones can be twisted into a-helixes, even in the gas phase in the absence of any solvent." A protein function is determined more directly by its three-dimensional structure and dynamics than by its sequence of amino acids. Three-dimensional structures are strongly influenced by weak non-covalent interactions between side functionalities, but the central importance of these weak interactions is by no means limited to structural effects. Life relies on biological specificity, which arises from the fact that individual biomolecules communicate through non-covalent interactions." " Molecular and chiral recognition rely on... 

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