P- Sheet

Figure Bl.17.11. Reconstructed density of an a,p-tiibulin protein dimer as obtained from electron crystallography (Nogales etal 1997). Note the appearance of the p-sheets ((a), marked B) and the a-helices ((b), marked H) in the density. In particular the right-handed a-helix H6 is very clear. Pictures by courtesy of E Nogales and Academic Press.

Circular dicliroism has been a useful servant to tire biophysical chemist since it allows tire non-invasive detennination of secondary stmcture (a-helices and P-sheets) in dissolved biopolymers. Due to tire dissymmetry of tliese stmctures (containing chiral centres) tliey are biaxial and show circular birefringence. Circular dicliroism is tlie Kramers-Kronig transfonnation of tlie resulting optical rotatory dispersion. The spectral window useful for distinguishing between a-helices and so on lies in tlie region 200-250 nm and hence is masked by certain salts. The metliod as usually applied is only semi-quantitative, since tlie measured optical rotations also depend on tlie exact amino acid sequence. 

Figure C3.2.6. Zones associated witlr the distinctive decay of electronic coupling tlrrough a-helical against p-sheet stmctures in proteins. Points shown refer to specific rates in mtlrenium-modified proteins aird in tire photosyntlretic reaction centre. From Gray H B aird Wiirkler J R 1996 Electron trairsfer in proteins A . Rev. Biochem. 65 537.

Proteins or sections of proteins sometimes exist as random coils, an arrangement that lacks the regularity of the a helix or pleated p sheet... 

Fig. 9. A de novo designed P sheet protein, betabellin, formed by the dimerization of two identical four-stranded -sheets and a disulfide linking the two sheets. This model is for betabeUins 9 and later progenies the earher betabeUins contained a two-armed cross-linker connecting the sheets (51).

Fig. 1. The two principal elements of secondary stmcture in proteins, (a) The a-helix stabilized by hydrogen bonds between the backbone of residue i and i + 4. There are 3.6 residues per turn of helix and an axial translation of 150 pm per residue. represents the carbon connected to the amino acid side chain, R. (b) The P sheet showing the hydrogen bonding pattern between neighboring extended -strands. Successive residues along the chain point...

Attempts have also been made at predicting the secondary stmcture of proteins from the propensities for residues to occur in the a-helix or the P-sheet (23). However, the assignment of secondary stmcture for a residue only has an average accuracy of about 60%. A better success rate (70%) is achieved when multiple-aligned sequences having high sequence similarity are available. 

Secondary Structure. The silkworm cocoon and spider dragline silks are characterized as an antiparaHel P-pleated sheet wherein the polymer chain axis is parallel to the fiber axis. Other silks are known to form a-hehcal (bees, wasps, ants) or cross- P-sheet (many insects) stmctures. The cross-P-sheets are characterized by a polymer chain axis perpendicular to the fiber axis and a higher serine content. Most silks assume a range of different secondary stmctures during processing from soluble protein in the glands to insoluble spun fibers. 

Figure 2.5 Schematic illustrations of antiparallel (3 sheets. Beta sheets are the second major element of secondary structure in proteins. The (3 strands are either all antiparallel as in this figure or all parallel or mixed as illustrated in following figures, (a) The extended conformation of a (3 strand. Side chains are shown as purple circles. The orientation of the (3 strand is at right angles to those of (b) and (c). A p strand is schematically illustrated as an arrow, from N to C terminus, (bj Schematic illustration of the hydrogen bond pattern in an antiparallel p sheet. Main-chain NH and O atoms within a p sheet are hydrogen bonded to each other.

Beta (P) sheets usually have their p strands either parallel or antiparallel... 

Figure 2.6 Parallel p sheet, (a) Schematic diagram showing the hydrogen bond pattern in a parallel p sheet, (b) Ball-and-stlck version of (a). The same color scheme is used as in Figure 2.5c. (c) Schematic diagram illustrating the pleat of a parallel p sheet.

Figure 2.7 (a) Illustration of the twist of (3 sheefs. Befa sfrands are drawn as arrows from the amino end to the carboxy end of the p strand in this schematic drawing of fhe protein thioredoxin from E. coli, fhe sfrucfure of which was defermined in the laboratory of Carl Branden, Uppsala, Sweden, fo 2.8 A resolution. The mixed p sheet is viewed from one of ifs ends, (b) The hydrogen bonds between the P strands in the mixed p sheet of fhe same profein. [(a) Adapfed from B. Furugren.]... 

Beta strands can also combine into mixed P sheets with some P strand pairs parallel and some antiparallel. There is a strong bias against mixed P sheets only about 20% of the strands inside the p sheets of known protein structures have parallel bonding on one side and antiparallel bonding on the other. Figure 2.7 illustrates how the hydrogen bonds between the p strands are arranged in a mixed P sheet. 

As they occur in known protein structures, almost all P sheets—parallel, antiparallel, and mixed—have twisted strands. This twist always has the same handedness as that shown in Figure 2.7, which is defined as a right-handed twist. 

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... 

Figure 2.15 The Greek key motif is found in antiparallel p sheets when four adjacent p strands are arranged in the pattern shown as a topology diagram in (a). The motif occurs in many p sheets and is exemplified here by the enzyme Staphylococcus nuclease (b). The four p strands that form this motif are colored red and blue.

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. 

This motif is called a beta-alpha-beta motif (Figure 2.17) and is found as part of almost every protein structure that has a parallel p sheet. For example, the molecule shown in Figure 2.10b, triosephosphate isomerase, is entirely built up by repeated combinations of this motif, where two successive motifs share one p strand. Alternatively, it can be regarded as being built up from four consecutive p-a-p-a motifs. 

Figure 2.17 Two adjacent parallel p strands are usually connected by an a helix from the C-termlnus of strand 1 to the N-termlnus of strand 2. Most protein structures that contain parallel p sheets are built up from combinations of such p-a-P motifs. Beta strands are red, and a helices are yellow. Arrows represent P strands, and cylinders represent helices, (a) Schematic diagram of the path of the main chain, (b) Topological diagrams of the P-a-P motif.

A survey of all known structures in 1991 showed that only those eight arrangements shown in Figure 2.21a occurred either as a complete p sheet or as a fragment of a p sheef with more than four strands. The number of times that these complex motifs occurred were 65, 29, 23, 11, 9, 3, 2, 1 for (i) to... 

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.

On the basis of simple considerations of connected motifs, Michael Leviff and Cyrus Chothia of the MRC Laboratory of Molecular Biology derived a taxonomy of protein structures and have classified domain structures into three main groups a domains, p domains, and a/p domains. In ct structures the core is built up exclusively from a helices (see Figure 2.9) in p structures the core comprises antiparallel p sheets and are usually two P sheets packed... 

The interiors of protein molecules contain mainly hydrophobic side chains. The main chain in the interior is arranged in secondary structures to neutralize its polar atoms through hydrogen bonds. There are two main types of secondary structure, a helices and p sheets. Beta sheets can have their strands parallel, antiparallel, or mixed. 

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. 

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