Hairpin p motif

Hairpin p motif, also called pp hairpin, which consists of two sequential antiparallel P-strands connected by a tight reverse turn. This motif changes the direction of antiparallel P-sheet structures. 

Mrksich, M., M.E. Parks, and P.B. Dervan. Hairpin peptide motif A new class of oligopeptides for sequence-specific recognition in the minor-groove of double-helical DNA. J. Am. Chem. Soc. 1994, 116, 7983-7988. 

Figure 4.8 Super-secondary structures found in proteins (a) P-a-P motifs (b) anti-parallel P-sheets connected by hairpin loops (c) a-a motifs. (From Voet and Voet, 2004. Reproduced with permission from John Wiley Sons., Inc.)...

FIGURE 3.12 Supersecondary structures found in proteins (a) p—a—p motif (b) antiparallel p-sheets connected by hairpin loops and (c) Qc—Qc motif. 

There is a natural hierarchy in proteins (see Figure 15.1) which allows the complex three-dimensional structure to be simplified and categorized as combinations of smaller motifs. At the atom level there are patterns of side-chain interactions at the backbone level we see formation of secondary structure (a helix, P sheet and yS turn) and loop families these combine to give supersecondary structures (e.g. P hairpins) and motifs (e.g. Greek key) and ultimately the whole tertiary and quaternary structure. In this chapter we present an overview of current patterns which are observed... 

Fig. 15.13. Ribbon diagrams [54] of examples of the three basic types of two-stranded p motifs, a antiparallel, hairpin from penicillopepsin residues 151 to 168 (3 APP). This has -Hi connectivity using the nomenclature in Section 15.4.2.1 b parallel. PaP unit from triose phosphate isomerase residues 6 to 42 (ITIM [46]) with -HlX connectivity, c intersheet connection from y-crystallin residues 34 to 47 (IGCR)...

Figure 2.14 shows examples of both cases, an isolated ribbon and a p sheet. The isolated ribbon is illustrated by the structure of bovine trypsin inhibitor (Figure 2.14a), a small, very stable polypeptide of 58 amino acids that inhibits the activity of the digestive protease trypsin. The structure has been determined to 1.0 A resolution in the laboratory of Robert Huber in Munich, Germany, and the folding pathway of this protein is discussed in Chapter 6. Hairpin motifs as parts of a p sheet are exemplified by the structure of a snake venom, erabutoxin (Figure 2.14b), which binds to and inhibits... 

The hairpin motif is a simple and frequently used way to connect two antiparallel p strands, since the connected ends of the p strands are close together at the same edge of the p sheet. How are parallel p strands connected If two adjacent strands are consecutive in the amino acid sequence, the two ends that must be joined are at opposite edges of the p sheet. The polypeptide chain must cross the p sheet from one edge to the other and connect the next p strand close to the point where the first p strand started. Such CTossover connections are frequently made by a helices. The polypeptide chain must turn twice using loop regions, and the motif that is formed is thus a p strand followed by a loop, an a helix, another loop, and, finally, the second p strand. 

Figure 2.21 illustrates the 24 possible ways in which two adjacent p hairpin motifs, each consisting of two antiparallel p strands connected by a loop region, can be combined to make a more complex motif. 

Figure 2.21 Two sequentially adjacent hairpin motifs can be arranged in 24 different ways into a p sheet of four strands, (a) Topology diagrams for those arrangements that were found in a survey of all known structures in 1991. The Greek key motifs in (1) and (v) occurred 74 times, whereas the arrangement shown in (viii) occurred only once, (b) Topology diagrams for those 16 arrangements that did not occur in any structure known at that time. Most of these arrangements contain a pair of adjacent parallel P strands.

Figure S.6 Schematic and topological diagrams of the folding motif in neuraminidase from influenza virus The motif is built up from four antiparallel P strands joined by hairpin loops, an up-and-down open P sheet.

We saw in Chapter 2 that the Greek key motif provides a simple way to connect antiparallel p strands that are on opposite sides of a barrel structure. We will now look at how this motif is incorporated into some of the simple antiparallel P-barrel structures and show that an antiparallel P sheet of eight strands can be built up only by hairpin and/or Greek key motifs, if the connections do not cross between the two ends of the p sheet. 

Figure 5.10 Idealized diagrams of the Greek key motif. This motif is formed when one of the connections of four antiparallel fi strands is not a hairpin connection. The motif occurs when strand number n is connected to strand + 3 (a) or - 3 (b) instead of -r 1 or - 1 in an eight-stranded antiparallel P sheet or barrel. The two different possible connections give two different hands of the Greek key motif. In all protein structures known so far only the hand shown in (a) has been observed.

The polypeptide chain is folded into two domains (Figure 11.7), each of which contains about 120 amino acids. The two domains are both of the antiparallel p-barrel type, each containing six p strands with the same topology (Figure 11.8). Even though the actual structure looks complicated, the topology is very simple, a Greek key motif (strands 1-4) followed by an antiparallel hairpin motif (strands 5 and 6). 

Figure 11.8 Topology diagrams of the domain structure of chymotrypsin. The chain is folded into a six-stranded antiparallel p barrel arranged as a Greek key motif followed by a hairpin motif.

The classic zinc fingers, the DNA-binding properties of which are discussed in Chapter 10, are small compact domains of about 30 residues that fold into an antiparallel p hairpin followed by an a helix. All known classic zinc fingers have a zinc atom bound to two cysteines in the hairpin and two histidines in the helix, creating a sequence motif common to all zinc finger genes. In the absence of zinc the structure is unfolded. 

Fig. 3.6 Polyamide-DNA binding motifs targeting longer DNA sequences. Overlapped and slipped homodimers depending on the sequence context, six-ring polyamides with central p-Ma residues can bind to DNA as fully overlapped homodimers, recognizing 11 bp, or as slipped homodimers, recognizing 13 bp. Extended hairpin extended conformation increases binding site size (to 9 bp) and enhances binding affinity. Cooperative dimer a cooperatively binding hairpin polyamide can...

The 42-residue peptide KO-42 folds in solution into a hairpin helix-loop-helix motif that dimerizes to form a four-helix bundle. On the surface of the folded motif there are six histidines with assigned piC values in the range 5.2 to 7.2 (Fig. 1) and the second-order rate constant for the hydrolysis of mono-p-nitro-phenyl fumarate is 1140 times larger than that of the 4-methylimidazole-cataly-zed reaction at pH 4.1 and 290 K [13]. The reaction mechanism was found to be pH dependent as the kinetic solvent isotope effect was 2.0 at pH 4.7 and 1.0 at pH 6.1 and the pH dependence showed that the reaction rate depended on residues in their unprotonated form with piCj, values around 5. It was thus established that there are functional cooperative reactive sites that contain protonated and unprotonated His residues. 

Frequently recurring substructures or folds are collectively termed supersecondary structures or motifs. These are combinations of a and/or j8 structure. A simple example is a /8 hairpin, consisting of two antiparallel strands joined by a loop of three to five residues (Figure 1.12). This frequently occurs in antiparallel P sheet. Such sheet frequently contains four p strands connected as in Figure 1.13 in a motif called a Greek key (or meander, which is the Greek word for the pattern) because it is reminiscent of the Greek decorative motif, or six strands described as a jellyroll. 

There are six ribozymes that have been successfully modified and/or adapted for use in therapeutic and functional genomic applications. These are the group I introns, RNAse P, the hammerhead and hairpin motifs, the hepatitis delta ribozyme and the reverse splicing reaction of group II introns. Each of these ribozymes requires a divalent metal cation for activity (usually Mg++), which may participate in the chemistry of the cleavage/ligation reaction and/or may be important for maintaining the structure of the ribozyme. 

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