Up-and-down p barrels

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. 

Up-and-down p barrels in which successive P strands are added adjacent to the previous strand until the P barrel is closed (eight antiparaUel P strands in P barrels or six small sheets, each with four p strands in superbarrels). 

Jelly roll barrels in which any even number of P strands (greater than four P strands) form a jelly roll barrel with equal number of connections across the top and bottom of the barrel. The antiparaUel up-and-down p barrel is the simplest organization. 

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. 

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.

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. 

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... 

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... 

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. 

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... 

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