P strands antiparallel

Figure 2.8 Adjacent antiparallel P strands are joined by hairpin loops. Such loops are frequently short and do not have regular secondary structure. Nevertheless, many loop regions in different proteins have similar structures, (a) Histogram showing the frequency of hairpin loops of different lengths in 62 different proteins, (b) The two most frequently occurring two-residue hairpin loops Type I turn to the left and Type II turn to the right. Bonds within the hairpin loop are green, [(a) Adapted from B.L. Sibanda and J.M. Thornton, Nature 316 170-174, 1985.]...

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. 

The p-a-P motif, which consists of two parallel p strands joined by an a helix, occurs in almost all structures that have a parallel p sheet. Four antiparallel p strands that are arranged in a specific way comprise the Greek key motif, which is frequently found in structures with antiparallel p sheets. 

Figure 4.5 The polypeptide chain of the enzyme pyruvate kinase folds into several domains, one of which is an a/p barrel (red). One of the loop regions in this barrel domain is extended and comprises about 100 amino acid residues that fold into a separate domain (blue) built up from antiparallel P strands. The C-terminal region of about 140 residues forms a third domain (green), which is an open twisted a/p structure.

In this structure the loop regions adjacent to the switch point do not provide a binding crevice for the substrate but instead accommodate the active-site zinc atom. The essential point here is that this zinc atom and the active site are in the predicted position outside the switch point for the four central parallel p strands, even though these p strands are only a small part of the total structure. This sort of arrangement, in which an active site formed from parallel p strands is flanked by antiparallel p strands, has been found in a number of other a/p proteins with mixed p sheets. 

Figure S.l The enzyme superoxide dismutase (SOD). SOD is a P structure comprising eight antiparallel P strands (a). In addition, SOD has two metal atoms, Cu and Zn (yellow circles), that participate in the catalytic action conversion of a superoxide radical to hydrogen peroxide and oxygen. The eight p strands are arranged around the surface of a barrel, which is viewed along the barrel axis in (b) and perpendicular to this axis in (c). [(a) Adapted from J.S. Richardson. The stmcture of SOD was determined in the laboratory of J.S. and D.R. Richardson, Duke University.)...

Figure S.3 Schematic diagram of the structure of human plasma retinol-binding protein (RBP), which is an up-and-down P barrel. The eight antiparallel P strands twist and curl such that the structure can also be regarded as two p sheets (green and blue) packed against each other. Some of the twisted p strands (red) participate in both P sheets. A retinol molecule, vitamin A (yellow), is bound inside the barrel, between the two P sheets, such that its only hydrophilic part (an OH tail) is at the surface of the molecule. The topological diagram of this stmcture is the same as that in Figure 5.2. (Courtesy of Alwyn Jones, Uppsala, Sweden.)...

There is a second family of small lipid-binding proteins, the P2 family, which include among others cellular retinol- and fatty acid-binding proteins as well as a protein, P2, from myelin in the peripheral nervous system. However, members of this second family have ten antiparallel p strands in their barrels compared with the eight strands found in the barrels of the RBP superfamily. Members of the P2 family show no amino acid sequence homology to members of the RBP superfamily. Nevertheless, their three-dimensional structures have similar architecture and topology, being up-and-down P barrels. 

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. 

Assume that we have eight antiparallel p strands arranged in a barrel structure. We decide that we want to connect strand number n to an antiparallel strand at the same end of the barrel. We do not want to connect it to strand number n -e 1 as in the up-and-down barrels just described, nor do we want to connect it to strand number n - 1 which is equivalent to turning the up-and-down barrel in Figure 5.2 upside down. What alternatives remain ... 

Figure S.12 Schematic diagram of the path of the polypeptide chain In one domain (the blue region in Figure 5.11) of the y-crystallln molecule. The domain structure is built up from two P sheets of four antiparallel p strands sheet 1 from p strands 1, 2, 4, and 7 and sheet 2 from strands 3, 5, 6, and 8.

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 2.7 (a) The P-bend or p-turn is often found between two stretches of antiparallel p-strands. (b) It is stabilized in part by hydrogen bonding between the C=0 bond and the NH groups of the peptide bonds at the neck of the turn... 

The template used for generating P-sheet structures described in this section is based on the structure of gramicidin S (1, Scheme 1). Gramicidin S is a head-to-tail cyclic decapeptide discovered over 50 years ago and has the sequence c[-Val-Om-Leu-D-Phe-Pro-]2. 13 The tertiary structure of gramicidin S has since been elucidated and found to exist in a P-sheet/p-turn conformation. 14,15 As shown in Scheme 1, two antiparallel P-strands containing the Val-Om-Leu sequence are held in place by two type II P-tums defined by the D-Phe-Pro sequence. Val and Leu residues occupy H-bonded sites while Orn residues are located in non-H-bonded sites. 

Gramicidin S is a symmetric decapeptide (sequence Val-Om-Leu-dPhe-Pro-Val-Om-Leu-dPhe-Pro) composed of two antiparallel p-strands linked by two type ir p-turns. 

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