Up-and-down barrel

Figure S.2 Schematic and topological diagrams of an up-and-down fi barrel. The eight p strands are all antiparallel to each other and are connected by hairpin loops. Beta strands that are adjacent in the amino acid sequence are also adjacent in the three-dimensional structure of up-and-down barrels.

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 ... 

Up-and-down barrels are the simplest structures. Each p strand is connected to the next strand by a short loop region. Eight p strands arranged... 

In rhino viruses there are depressions, or "canyons," which are 25 A deep and 12 to 30 A wide and which encircle the protrusions (Figure 16.15b). One wall of the canyons is lined by residues from the base of VPl. The structure of VPl is such that the barrel is open at the base and permits access to the hydrophobic interior of the barrel, as in the up-and-down barrel structure of the retinol-binding protein described in Chapter 5. 

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. 

FIGURE 12,38. Motifs in protein architecture, (a) Up-and-down barrel, (b) jelly-roll motif, and (c) (/lajg barrel. Compare these with (d), (e), and (f), which is what the folding looks like in three dimensions. 

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]...

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... 

A large number of the all-/8 structures arrange their strands to form barrel-like or sandwich structure. The simplest of these arrangements is the up-and-down barrel or clam motif found in the retinol binding superfamily of proteins (Fig. 12a) where each strand adds to the next in an antiparallel manner until the barrel is complete. In this group of proteins the interior of the barrel provides a binding site for hydrophobic ligands. 

The simplest topology is obtained if each successive p strand is added adjacent to the previous strand until the last strand is joined by hydrogen bonds to the first strand and the barrel is closed (Figure 5.2). These are called up-and-down P sheets or barrels. The arrangement of p strands is similar to that in the a/P-barrel structures we have just described in Chapter 4, except that here the strands are antiparallel and all the connections are hairpins. The structural and functional versatility of even this simple arrangement will be illustrated by two examples. 

Tlie retinol-binding protein binds retinol inside an up-and-down fi barrel... 

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. 

A second example of up-and-down p sheets is the protein neuraminidase from influenza virus. Here the packing of the sheets is different from that in RBP. They do not form a simple barrel but instead six small sheets, each with four P strands, which are arranged like the blades of a six-bladed propeller. Loop regions between the p strands form the active site in the middle of one side of the propeller. Other similar structures are known with different numbers of the same motif arranged like propellers with different numbers of blades such as the G-proteins discussed in Chapter 13. 

It is easy to see from Figure 5.10 that there are only two alternatives. We can connect it either to strand number n + 3 or to n - 3. Both cases require only short loop regions that traverse the end of the barrel. How do we now continue the connections The simplest way to connect the strands that were skipped over is to join them by up-and-down connections, as illustrated in Figure 5.10. 

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. 

To illustrate how this rather complicated structure is built up, we will start by wrapping a piece of string around a barrel as shown in Figure S.16. The string goes up and down the barrel four times, crosses over once at the bottom and twice at the top of the barrel. This configuration is the basic pattern for the jelly roll motif. 

The second protein in the membrane of influenza vims, neuraminidase, does not belong to any of these three groups of barrel structures. Instead, it forms a propeller-like structure of 24 p strands, arranged in six similar motifs that form the six blades of the propeller. Each motif is a p sheet of 4 up-and-down-connected p strands. The enzyme active site is formed by loop regions on one side of the propeller. 

Each subunit of the trimeric porin molecule from R. capsulatus folds into a 16-stranded up and down antiparallel P barrel in which all p strands form... 

A. Up-and-down /3 barrels Papain domain 2 Soybean trypsin inhibitor Catalase domain 1... 

Domain 1 up-and-down fi barrel Domain 2 miscellaneous antiparallel a Domain 3 doubly wound parallel fi sheet... 

Figure 89c schematizes the globin structure as a twisted cylinder of helices, analogous to the antiparallel /8 barrels to be discussed in Section III,D. The up-and-down helix bundle structures are of course also readily described as cylinders, so that this schema makes the... 

The first type of anti parallel /3 barrel, in analogy with the first type of helix bundle, has simple up and down +1,+ 1,+ 1 connections all around. Although it is relatively unusual for a barrel to be composed entirely of up-and-down strands, many of the larger barrels and sheets have four- to six-stranded sections of simple up-and-down topology... 

Fig. 95. Papain domain 2 as an example of an up-and-down antiparallel /3 barrel, (a) a-Carbon stereo, viewed from one side of the barrel (b) backbone schematic, viewed as in a.

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