P sheet packings

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... 

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 15.24 Ribbon diagram (a) and topology diagram (b) of the fibronectin type III domain, which is composed of a three-stranded and a four-stranded p sheet packed together as a compressed barrel.

The immunoglobulin fold is best described as two antiparallel p sheets packed tightly against each other 304... 

In most proteins the small number of ways. The connections between secondary structures obey a set of empirical topological rules in almost all cases.. . Subsequently, it was argued that these similarities arise from the intrinsic physical and chemical properties of proteins, and a great deal of work was carried out to demonstrate that this is the case [emphasis added]. 

P Sheets pack together in proteins with individually variable extents of twist [67, 113, 114], In order to pack well it is necessary for fi sheets with different twists and residue compositions to pack so that the central part of each P sheet is closely packed as the two sheets make contact. When the twists of the P sheets are approximately 0°, two sheets are complementary to one another and can pack readily. When, however, the two P sheets have different degrees of twist, one P sheet needs to be rotated with respect to the other in order to optimize the overlap. If the main structure of a domain is p sheet, then it is likely that the domain will contain two such p sheets and that they will lie either almost parallel or almost perpendicular to each other (Figure 18) [115]. 

In barrels the hydrophobic side chains of the a helices are packed against hydrophobic side chains of the p sheet. The a helices are antiparallel and adjacent to the p strands that they connect. Thus the barrel is provided with a shell of hydrophobic residues from the a helices and the p strands. 

The packing interactions between a helices and p strands are dominated by the residues Val (V), He (I), and Leu (L), which have branched hydrophobic side chains. This is reflected in the amino acid composition these three amino acids comprise approximately 40% of the residues of the P strands in parallel P sheets. The important role that these residues play in packing a helices against P sheets is particularly obvious in a/P-barrel structures, as shown in Table 4.1. 

Third, in open-sheet structures the a helices are packed against both sides of the p sheet. Each p strand thus contributes hydrophobic side chains to pack against a helices in two similar hydrophobic core regions, one on each side of the p sheet. 

Cohen, F.E., Sternberg, M.J.E., Taylor, W.R, Analysis and prediction of the packing of a-helices against a p-sheet in the tertiary structure of globular proteins. 

Antiparallel beta (P) structures comprise the second large group of protein domain structures. Functionally, this group is the most diverse it includes enzymes, transport proteins, antibodies, cell surface proteins, and virus coat proteins. The cores of these domains are built up by p strands that can vary in number from four or five to over ten. The P strands are arranged in a predominantly antiparallel fashion and usually in such a way that they form two P sheets that are joined together and packed against each other. 

The p sheets have the usual twist, and when two such twisted p sheets are packed together, they form a barrel-like structure (Figure 5.1). Antiparallel P structures, therefore, in general have a core of hydrophobic side chains inside the barrel provided by residues in the P strands. The surface is formed by residues from the loop regions and from the strands. The aim of this chapter is to examine a number of antiparallel p structures and demonstrate how these rather complex structures can be separated into smaller comprehensible motifs. 

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.)...

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. 

The basic structural unit of these two-sheet p helix structures contains 18 amino acids, three in each p strand and six in each loop. A specific amino acid sequence pattern identifies this unit namely a double repeat of a nine-residue consensus sequence Gly-Gly-X-Gly-X-Asp-X-U-X where X is any amino acid and U is large, hydrophobic and frequently leucine. The first six residues form the loop and the last three form a p strand with the side chain of U involved in the hydrophobic packing of the two p sheets. The loops are stabilized by calcium ions which bind to the Asp residue (Figure S.28). This sequence pattern can be used to search for possible two-sheet p structures in databases of amino acid sequences of proteins of unknown structure. 

Figure 9.17 Schematic diagram illustrating the tetrameric stmcture of the pS3 oligomerization domain. The four subunits have different colors. Each subunit has a simple structure comprising a p strand and an a helix joined by a one-residue turn. The tetramer is built up from a pair of dimers (yellow-blue and red-green). Within each dimer the p strands form a two-stranded antiparallel p sheet which provides most of the subunit interactions. The two dimers are held together by interactions between the four a helices, which are packed in a different way from a four-helix bundle. (Adapted from P.D. Jeffrey et al.. Science 267 1498-1502, 1995.)...

Figure 15.10 Schematic diagrams of the packing of the four-stranded p sheets of the constant domains Chi and Cl in an Fab fragment of IgG. The sheets are viewed perpendicular to the p strands in (a) and end-on in (b), where the four-stranded p sheets are blue.

The variable domains associate in a strikingly different manner. It is obvious from Figure 15.11 that if they were associated in the same way as the constant domains, via the four-stranded p sheets, the CDR loops, which are linked mainly to the five-stranded p sheet, would be too far apart on the outside of each domain to contribute jointly to the antigen-binding site. Thus in the variable domains the five-stranded p sheets form the domain-domain interaction area (Figure 15.11). Furthermore, the relative orientation of the p strands in the two domains is closer to parallel than in the constant domains and the curvature of the five-stranded p sheets is such that they do not pack... 

The canonical jelly roll barrel is schematically illustrated in Figure 16.13. Superposition of the structures of coat proteins from different viruses show that the eight p strands of the jelly roll barrel form a conserved core. This is illustrated in Figure 16.14, which shows structural diagrams of three different coat proteins. These diagrams also show that the p strands are clearly arranged in two sheets of four strands each P strands 1, 8, 3, and 6 form one sheet and strands 2, 7, 4, and 5 form the second sheet. Hydrophobic residues from these sheets pack inside the barrel. 

Figure 16.18 A dimer is the basic unit that builds up the capsid of bacteriophage MS2. The two subunits (red and biue) are arranged so that the dimer has a p sheet of 10 antiparaliel strands on one side and the hairpins and a heiices on the other side. The heiices from one subunit pack against p strands from the other subunit and vice versa. (Adapted from a diagram provided by L. Liljas.)...

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