Greek key motif

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.

Figure 2.16 Suggested folding pathway from a hairpinlike structure to the Greek key motif. Beta strands 2 and 3 fold over such that strand 2 is aligned adjacent and antiparallel to strand 1. The topology diagram of the Greek key shown here is the same as in Figure 2.15a but rotated 180° in the plane of the page.

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 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. 

Greek key motifs occur frequently in antiparallel /3 structures... 

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.

Figure S.IS Schematic diagram (a) and topology diagram (b) for the y-crystallin molecule. The two domains of the complete molecule have the same topology each is composed of two Greek key motifs that are joined by a short loop region, [(a) Adapted from T. Blundell et ah. Nature 289 171-777, 1981.]...

A relevant question to ask at this stage is, do the topological identities displayed in the diagram reflect structural similarity We can now see that topologically the polypeptide chain is divided into four consecutive Greek key motifs arranged in two domains. How similar are the domain structures to each other, and how similar are the two motifs within each domain ... 

This structural similarity is also reflected in the amino acid sequences of the domains, which show 40% identity. They are thus clearly homologous to each other. The motif structures within the domains superpose equally well but their sequence homology is less, being around 30% between motifs 1 and 2 and 20 Xi between 3 and 4. This study, however, clearly shows that the topological description in terms of four Greek key motifs is also valid at the structural and amino acid sequence levels. 

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

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.

Figure IS. 7 The constant domains of immunoglobulins are folded into a compressed antiparallel p banel built up from one three-stranded p sheet packed against a four-stranded sheet (a). A topological diagram (b) shows the connected Greek key motifs of this fold.

Figure 16.21 Structure of one subunit of the core protein of Slndbls virus. The protein has a similar fold to chymotrypsin and other serine proteases, comprising two Greek key motifs separated by an active site cleft. The C-terminus of the protein is bound in the catalytic site, making the coat protein inactive (Adapted from S. Lee et al., Structure 4 531-541, 1996.)...

Type I copper is present at the active site of blue copper proteins (BCP see chapter by Nersissian and Shipp, this volume) where it is involved in the transfer of a single electron, as well as in multicopper enzymes (Gray et al., 2000 Malmstrdm, 1994 Randall et al., 2000 Sykes, 1991) (see Section V). BCP are single-domain proteins with a (3-barrel fold defined by two (3-sheets that can contain 6 to 13 strands following a Greek-key motif (Fig. 1) (Adman, 1991 Messerschmidt, 1998 Murphy ei a/., 1997 Sykes, 1991). These proteins are stable in both the reduced, Cu(I), and the oxidized, Cu(II), forms. 

Domain 3 is simpler. It is a classic immunoglobulin fold (Fig. 3 see Color Insert) connected to domain 1 by a single polypeptide chain. This fold contains Greek key motifs and is a seven-stranded antiparallel / barrel with hydrogen bonding that that is broken into a three-stranded sheet packed against a four-stranded sheet. There are three short three-residue / strands that form an additional small sheet. 

FIGURE 12.35. Motifs in protein architecture, (a) The / meander and (b) the Greek key motif. On the left is shown a commonly used simplified diagram, while on the right is shown how the folding occurs in three dimensions. Note the three dimensionality of the Greek key motif, (c) The Pa/l motif with the helix above the plane (marked by broken lines). 

Greek key motif A geometric motif found in Greek pottery that can be used to describe a certain type of folding pattern of a protein structure. 

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