Hairpin 1 motif

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.

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.

To prevent insolubility resulting from uncontrolled aggregation of extended strands, two adjacent parallel or antiparallel yS-peptide strands can be connected with an appropriate turn segment to form a hairpin. The / -hairpin motif is a functionally important secondary structural element in proteins which has also been used extensively to form stable and soluble a-peptide y9-sheet arrangements in model systems (for reviews, see [1, 4, 5] and references therein). The need for stable turns that can bring the peptide strands into a defined orientation is thus a prerequisite for hairpin formation. For example, type F or II" turns formed by D-Pro-Gly and Asn-Gly dipeptide sequences have been found to promote tight a-pep-tide hairpin folding in aqueous solution. Similarly, various connectors have been... 

Dervan. Tandem hairpin motif for recognition in the minor groove of DNA by pyrrole-imidazole polyamides. Chem.-Eur. 

Fig. 4. The self-cleaving hairpin motif from the satellite RNA of tobacco ringspot virus (sTobRV). The arrow indicates the cleavage site. The numbers in brackets indicate the nucleotide positions within the sTobRV satellite RNA...

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. 

High-pressure FTIR measurements in 2003 [97] indicated that C H 0 bonds help stabilize p-sheets. These interactions were also instrumental in the formation of extended p-strands in a chain containing D-chiral residues [98], A helical hairpin motif was attributed [99] to CH- -O bonds between the side chains of one helix and the backbone of another in 2001. The large number (75) of CH O bonds exceeds the 49 conventional intersubunit H-bonds, indicating that the former contacts determine association and orientation of transmembrane helices in PSI [100]. A detailed survey [101] indicated that these bonds can affect the Trp rotation angle in proteins. These bonds were considered potentially as a driving force for ligand selectivity, as noted in the hydrophobic pocket of retinoic add receptor RARy [102]. 

A /3-hairpin motif shows residues 1-7 in well-conserved structural positions relative to the EF hand (Figure 1). Residue 9 typically moves and delivers two oxygens from a carboxylate to take up the site previously taken by residue 12. Divalent calcium can also be bound by a structurally similar loop bound by an a helix and [3 strand. Overall, the residues 1, 3, 5, and 9 are conserved in all of these structures and appear sufficient to define the Ca binding motif. Putative Ca binding sequences in integrins resemble those found in EF hands and have been termed EF hand-like (Figure 1). The a helix//3 strand defined motif common to integrins also lacks the need for residue 12. 

Our recent NMR study of the 24mer hairpin motif comprising largely the symmetrical internal loop revealed that a unique and stable structure is formed only in the presence of Mg2+ ions, which seem to bind specifically in the internal loop region. Unfortunately, this construct had a large propensity for duplex formation and we did not consider the NMR data of sufficient quality to allow a high resolution structure determination. This particular problem could be circumvented by making the transition from the kinetically favored hairpin... 

Hairpins can form when there are complementary sequences within the same strand but separated by a noncomplementaiy region, such as the sequence 5 -CGCGCGCGAAAGCGCGCG-3 where the central GAAA forms the loop and the imderlined bases at the termini form the stem (Fig. 5). If a hairpin is formed within the context of double-stranded DNA, the complementary strand can also fold into a hairpin, yielding a cruciform structin-e, or remain impaired. Such structures likely serve as binding sites for proteins. Fimthermore, the hairpin motif is one of the most common secondary structin-e elements observed in RNA (17). 

Ref. 91. American Chemical Society, 2005.) (b) A cartoon schematic of the hairpin motif. (Reproduced from Ref. 93. American... 

The X-ray crystal structure of MMOH from M. capsulatus (Bath) has been determined by Lippard et al at 2.2 A resolution [52, 53]. The X-ray diffraction data were collected at 4 The enzyme is a relatively flat molecule with approximate dimensions 60 x 100 x 200 A. The arrangement of the subunits is similar to the schematic drawing in Scheme 1. The two a-subunits contact one another and so do two P-subunits with more extensive contacts. The y-subunit lies on the outer edges of the molecule at the interface of the a-and p-subunit. The two apy protomers are related by a non-crystallographic two fold symmetry and form a heart-shaped molecule. There is a large canyon at the interface between the two aPy protomers. The secondary structure of the three subunits is primarily helical, with one small region of p-structure in the a-subunit. The a-subunit involves 18 helices and two P-hairpin motifs. The P-subunit has 12 helices. The y-... 

Sphingolipid-binding domain (SBD) A structural hairpin motif found in sequence-unrelated proteins that interact with sphingolipids. Discovered for the first time in HIV-1 surface envelope glycoprotein gpl20. 

The hairpin (i motif occurs frequently in protein structures... 

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