Greek key barrels

The commonest subgroup of antiparallel /3 barrel structures has a Greek key topology, with -3,+1,+1,-3 connections or a close variant. The first Greek key barrel structures were compared in Richardson et al. (1976), and they and the up-and-down barrels were described as categories in Richardson (1977). Figure 96 illustrates Cu,Zn superoxide dismutase as an example of a Greek key j8 barrel. 

There are 13 Greek key barrels in our sample, and 12 of them (all except staphylococcal nuclease) have the same handedness viewed from the outside, the Greek key pattern forms a counterclockwise swirl (see Fig. 97). The four barrels shown in Figure 81 have a more... 

The Greek key barrels have between 5 and 13 strands, but in all cases they enclose approximately the same cross-sectional area (see Section II,B). The cross sections are somewhat elliptical, with more flattening the more strands there are. For 8- to 10-stranded barrels, it is noticeable that the direction of the long axis of the cross-section twists from one end of the barrel to the other by close to 90° (see Fig. 99). 

Fig.6. Ribbon drawing of the Cu.ZnSOD monomer (M2SODD183N) showing the secondary structure elements arranged in the Greek-key barrel fold. The metal ions are represented by spheres of arbitrary dimensions (copper, light gray zinc, dark gray) (Band et al., 1998).

Fig. 15.26. Ribbon diagram [54] of the six-stranded Greek-key barrel in yS-trypsin (4 FTP). Strands 1 to 4 and strands 3 to 6 each form single (4,0) Greek keys...

Fig. 2. Ribbon diagram of the Cu2Zn2SOD monomer showing the secondary structures of the enzyme and the arrangement of the eight strands in the Greek-key barrel fold, (the P strands and loops are numbered following the conventions established in Refs. 28 and 41). The metal ions are represented as spheres of arbitrary radius. (A) Side view (B) top view highlighting the /3-barrel and the active site location.

Antiparallel p sheets are, as was described earUer, twisted, and they can pack to form a barrel with a hydrophobic core. Three structures are commonly found for -proteins these are the up-and-down barrel (Figure 22a), the Greek key barrel (Figure 22b) and the jelly-roll barrel (Figure 22c). Another motif, shown in Figure 22(d), has been found in pectate lyase [119], even though it was thought too unstable to exist. 

Figure 22 Sheet motifs (a) the up-and-down barrel (b) the Greek key barrel (c) the jelly-roll barrel and (d) the structure in pectate lyase [119]...

Greek key barrels in which eight antiparaUel p strands builds up Greek key motifs (two consecutive Greek key motifs with one of the connections CTossing one end of the barrel). 

The p class contains the parallel and antiparallel p structures. The p strands are usually arranged in two p sheets that pack against each other and form a distorted barrel structure. Three major types of p barrels exist, the up-and-down barrels, the Greek key barrels,and the jelly roll barrels (see Figure 6). Most known antiparallel p structures, including the... 

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.

We have now connected four adjacent strands of the barrel in a simple and logical fashion requiring only short loop regions. The result is the Greek key motif described in Chapter 2, which is found in the large majority of antiparallel (i structures. The two cases represent the two possible different hands, but in all structures known to us the hand that corresponds to the case where (i strand n is linked to (3 strand n + 3 as in Figure 5.10a is present. 

The remaining four strands of the barrel can be joined either by up-and-down connections before and after the motif or by another Greek key motif. We will examine examples of both cases. 

Figure S.14 The eight P strands in one domain of the crystallin structure in this idealized diagram are drawn along the surface of a barrel. From this diagram it is obvious that the p strands are arranged in two Greek key motifs, one (red) formed by strands 1-4 and the other (green) by strands 5-8. Notice that the p strands that form one motif contribute to both P sheets as shown in Figure 5.12.

The Greek key motifs can form jelly roll barrels... 

The number of possible ways to form antiparallel p structures is very large. The number of topologies actually observed is small, and most p structures fall into these three major groups of barrel structures. The last two groups—the Greek key and jelly roll barrels—include proteins of quite diverse function, where functional variability is achieved by differences in the loop regions that connect the p strands that build up the common core region. 

Most of the known antiparallel p structures, including the immunoglobulins and a number of different enzymes, have barrels that comprise at least one Greek key motif. An example is 7 crystallin, which has two consecutive Greek key motifs in each of two barrel domains. These four motifs are homologous in terms of both their three-dimensional structure and amino acid sequence and are thus evolutionarily related. 

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.

A closer examination of these essential residues, including the catalytic triad, reveals that they are all part of the same two loop regions in the two domains (Figure 11.10). The domains are oriented so that the ends of the two barrels that contain the Greek key crossover connection (described in Chapter 5) between p strands 3 and 4 face each other along the active site. The essential residues in the active site are in these two crossover connections and in the adjacent hairpin loops between p strands 5 and 6. Most of these essential residues are conserved between different members of the chymotrypsin superfamily. They are, of course, surrounded by other parts of the polypeptide chains, which provide minor modifications of the active site, specific for each particular serine proteinase. 

FIGURE 6.33 Examples of the so-called Greek key andparallel /3-barrel structure iu proteins. 

Domains 1 and 2 jellyroll Greek key /3 barrel Cytochrome b5 (Mathews et al., 1972)... 

HA1 jellyroll Greek key /3 barrel HA2 open-face /3 sandwich HA2 around 3-fold miscellaneous helix cluster Hemerythrin (Stenkamp et al., 1978), see Myohemerythrin Hemoglobin (Ladner et al., 1977)... 

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