Hairpin structures

Figure 17.11 Structure of EMPl dimer from x-ray crystallography. In the presence of EBP, the EMPl peptide forms a dimer. Each monomer (shown in red and blue) forms a p hairpin structure stabilized by hydrogen bonds (red dashes) and a disulfide bond (yellow).

Fig. 2.30 Comparison of antiparallel hairpin structures in / -peptides 120-122. (A) / -Pep-tides 120, 121 with a 12-membered R/S dini-pecotic (Nip or/ -HPro) turn segment (gray color). Summary of backbone-backbone and side-chain-side-chain NOEs collected in CD2CI2 and X-ray crystal structure of 121 (stereo-view) [154, 193], The intramolecular H-bond N" 0 distances are shown. The angles (N-H -O) are 170.8° (inner H-bond) and 1 72.3 ° (outer H-bond). (B) jS-Peptide 122 with...

In recent work, Balaram and coworkers have demonstrated that /9-amino acids can be tolerated at specific positions in the strands and turn segments of a-pep-tide hairpins [197, 198]. Induction of turn structure in tetrapeptides by incorporation of a / -amino acid has also been described [115]. Similarly, studies by Gell-man have shown that the dinipecotic acid heterochiral turn segment can be used to nucleate a-peptide hairpin structures [199]. 

Although their medium-resolution model was successful for a-helical proteins, folding P-hairpin structures have been difficult. In general, many off-lattice approaches have been tested, and although definitive proof does not exist in most cases, there appears to be a growing consensus that such off-lattice models are not sufficient. 

Rho-dependent transcription termination signals in E coll also appear to have a distinct consensus sequence, as shown in Figure 37—6. The conserved consensus sequence, which is about 40 nucleotide pairs in length, can be seen to contain a hyphenated or interrupted inverted repeat followed by a series of AT base pairs. As transcription proceeds through the hyphenated, inverted repeat, the generated transcript can form the intramolecular hairpin structure, also depicted in Figure 37-6. 

Fig. 10. Intrastrand Hgn-crosslink in T4-hairpin structures. Reproduced with permission from Ref. (40). Copyright 1996, American Chemical Society.

Single-stranded DNA or RNA may adopt hairpin structures in which the distance between two sequences is much shorter than in the absence of hairpin. Figure B9.4.1 shows two synthetic targets, both containing 45 nucleotides, but only the first one is able to form a hairpin via a loop of four thymines. The second one is used as a control. Both contain the complementary sequences for ethidium-13-mer and 11-mer-coumarin separated by the same number of bases. The efficiency of energy transfer from coumarin to ethidium is dose to zero for the control, whereas it is about 25% in the hairpin structure. This value is low but the spatial conformation of this particular three-way junction is only partially known, and the transfer efhdency depends on the relative orientation and/or distance between coumarin and ethidium. 

Fig. B9.4.1. Sequences of the 45-mer containing a hairpin structure and the control 45-mer (redrawn from Mergny et al.a)).

Nucleic acid structures and sequences primary and secondary structure of DNA fragments, translocation of genes between two chromosomes, detection of nucleic acid hybridization, formation of hairpin structures (see Box 9.4), interaction with drugs, DNA triple helix, DNA-protein interaction, automated DNA sequencing, etc. 

Schneider and Pochan (2002) have described a different system of peptides with alternating polar and hydrophobic residues composed of Val as an amino acid with high -sheet forming propensity and Lys as a modulator of pH-dependent self-assembly. Self-assembly was designed to be triggered by intramolecular folding into a /3-hairpin structure based on the stereochemistry of central Pro residues (Fig. 14.8). 

Stabilization of a P-hairpin structure can be achieved in two ways, promoting a stable (or restricted) turn structure (as done with mimetics) or linking the two arms either chemically, or, more naturally, by hydrophobic interactions. In an approach to utilizing both methods, a D-Pro-Gly linkage was used to stabilize a left-handed turn (type I or II ) and various charged and hydrophobic residues were used to stabilize the molecule and enhance the interaction between arms. I252"254 Examples of these peptides studied in nonaqueous solution by IR, VCD and NMR spectroscopy exhibit characteristics of well-formed hairpins. 255 Alternatively, in aqueous solution, IR, VCD, and ECD results for related peptides agree with the NMR interpretation of conformations characterized as hairpins stabilized at the turn and frayed at the ends. 256 These latter results also have a qualitative match with theoretical simulations. Recently, examples of hydrophobically stabilized hairpins studied by NMR spectroscopy have avoided use of a nonnatural amino acid. 257,258 ... 

The binding capacity of IRE-BP to the hairpin structures is controlled by the amount of iron. Low iron concentrations favor the formation of a binding competent form, high iron concentrations favor the formation of a binding incompetent form of IRE-BP. Both forms of the IRE-BP differ from each other in terms of their content of a 4Fe-4S cluster. Iron favors the insertion of the 4Fe-4S cluster into the protein and thereby transmits it into the binding incompetent state. In the presence of high levels of iron, the hairpin structures are not occupied, the mRNA can be degraded, and the level of TFR drops. 

Hie regulation of the ferritin concentration is also related to the iron concentration. Hie vulnerable point is not the stability of the mRNA, but rather of the initiation of translation. Hie mRNA for ferritin possesses a hairpin structure in the 5 - non-coding... 

Fig. 1.54 Principle of negative control of translation initiation by protein binding to mRNA. Proteins can negatively effect translation by binding to the sequences in the 5 non-translated region of their own or other mRNAs. The participating proteins are sequence-specific RNA binding proteins and recognize RNA sequences in hairpin structures or other secondary structures of RNA. The protein binding interferes with the scanning of ribosomes and prevents the translation of mRNA.

The formation of aptamer-substrate complexes was also followed by the use of redox-active intercalators73 (Fig. 12.18d). A nucleic acid hairpin structure that contained in its single-stranded loop the antithrombin base sequence was assembled on a Au electrode, and methylene blue was intercalated as a redox label in the double-stranded stem of the hairpin structure. The hairpin was, then, opened in the presence of thrombin, by generating the respective G-quadruplex-thrombin complex, and as a result, the redox label was removed from the nucleic structure, showing a decrease in the voltammetric response with the increase in the concentration of thrombin. This method enabled the analysis of thrombin with a detection limit that corresponded to... 

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