Protein structure 3-strands

The 3-sheet is another form of secondary structure in which all of the peptide bond components are involved in hydrogen bonding (Figure 2.7A). The surfaces of 3-sheets appear "pleated," and these structures are, therefore, often called "P-pleated sheets." When illus trations are made of protein structure, 3-strands are often visualized as broad arrows (Figure 2.7B). 

Beta strands can also combine into mixed P sheets with some P strand pairs parallel and some antiparallel. There is a strong bias against mixed P sheets only about 20% of the strands inside the p sheets of known protein structures have parallel bonding on one side and antiparallel bonding on the other. Figure 2.7 illustrates how the hydrogen bonds between the p strands are arranged in a mixed P sheet. 

As they occur in known protein structures, almost all P sheets—parallel, antiparallel, and mixed—have twisted strands. This twist always has the same handedness as that shown in Figure 2.7, which is defined as a right-handed twist. 

This motif is called a beta-alpha-beta motif (Figure 2.17) and is found as part of almost every protein structure that has a parallel p sheet. For example, the molecule shown in Figure 2.10b, triosephosphate isomerase, is entirely built up by repeated combinations of this motif, where two successive motifs share one p strand. Alternatively, it can be regarded as being built up from four consecutive p-a-p-a motifs. 

Figure 2.17 Two adjacent parallel p strands are usually connected by an a helix from the C-termlnus of strand 1 to the N-termlnus of strand 2. Most protein structures that contain parallel p sheets are built up from combinations of such p-a-P motifs. Beta strands are red, and a helices are yellow. Arrows represent P strands, and cylinders represent helices, (a) Schematic diagram of the path of the main chain, (b) Topological diagrams of the P-a-P motif.

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.

For each fold one searches for the best alignment of the target sequence that would be compatible with the fold the core should comprise hydrophobic residues and polar residues should be on the outside, predicted helical and strand regions should be aligned to corresponding secondary structure elements in the fold, and so on. In order to match a sequence alignment to a fold, Eisenberg developed a rapid method called the 3D profile method. The environment of each residue position in the known 3D structure is characterized on the basis of three properties (1) the area of the side chain that is buried by other protein atoms, (2) the fraction of side chain area that is covered by polar atoms, and (3) the secondary stmcture, which is classified in three states helix, sheet, and coil. The residue positions are rather arbitrarily divided into six classes by properties 1 and 2, which in combination with property 3 yields 18 environmental classes. This classification of environments enables a protein structure to be coded by a sequence in an 18-letter alphabet, in which each letter represents the environmental class of a residue position. 

Many structural components of the tight junctions (TJs) have been defined since 1992 [85-97]. Lutz and Siahaan [95] reviewed the protein structural components of the TJ. Figure 2.7 depicts the occludin protein complex that makes the water pores so restrictive. Freeze-fracture electronmicrographs of the constrictive region of the TJ show net-like arrays of strands (made partly of the cytoskeleton) circumscribing the cell, forming a division between the apical and the basolateral... 

Due to the ready accessibility of SH2 domains by molecular biology techniques, numerous experimentally determined 3D structures of SH2 domains derived by X-ray crystallography as well as heteronuclear multidimensional NMR spectroscopy are known today. The current version of the protein structure database, accessible to the scientific community by, e.g., the Internet (http //www.rcsb.org/pdb/) contains around 80 entries of SH2 domain structures and complexes thereof. Today, the SH2 domain structures of Hck [62], Src [63-66], Abl [67], Grb2 [68-71], Syp [72], PLCy [73], Fyn [74], SAP [75], Lck [76,77], the C- and N-terminal SH2 domain ofp85a [78-80], and of the tandem SH2 domains Syk [81,82], ZAP70 [83,84], and SHP-2 [85] are determined. All SH2 domains display a conserved 3D structure as can be expected from multiple sequence alignments (Fig. 4). The common structural fold consists of a central three-stranded antiparallel ft sheet that is occasionally extended by one to three additional short strands (Fig. 5). This central ft sheet forms the spine of the domain which is flanked on both sides by regular a helices [49, 50,60]. 

Protein structures are so diverse that it is sometimes difficult to assign them unambiguously to particular structural classes. Such borderline cases are, in fact, useful in that they mandate precise definition of the structural classes. In the present context, several proteins have been called //-helical although, in a strict sense, they do not fit the definitions of //-helices or //-solenoids. For example, Perutz et al. (2002) proposed a water-filled nanotube model for amyloid fibrils formed as polymers of the Asp2Glni5Lys2 peptide. This model has been called //-helical (Kishimoto et al., 2004 Merlino et al., 2006), but it differs from known //-helices in that (i) it has circular coils formed by uniform deformation of the peptide //-conformation with no turns or linear //-strands, as are usually observed in //-solenoids and (ii) it envisages a tubular structure with a water-filled axial lumen instead of the water-excluding core with tightly packed side chains that is characteristic of //-solenoids. 

The a-helix is the classic element of protein structure. A single a-helix can order as many as 35 residues whereas the longest strands include only about 15 residues, and one helix can have more influence on the stability and organization of a protein than any other individual structure element. a-Helices have had an immense influence on our understanding of protein structure because their regularity makes them the only feature readily amenable to theoretical analysis. 

A few other helical conformations occur occasionally in globular protein structures. The polyproline helix, of the same sort as one strand out of a collagen structure, has been found in pancreatic trypsin inhibitor (Huber et al., 1971) and in cytochrome c551 (Almassy and Dickerson, 1978). An extended e helix has been described as occurring in chymotrypsin (Srinivasan et al., 1976). In view of the usual variability and irregularity seen in local protein conformation it is unclear that either of these last two helix types is reliably distinguishable from simply an isolated extended strand however, the presence of prolines can justify the designation of polyproline helix. 

Large portions of most protein structures can be described as stretches of secondary structure (helices or /3 strands) joined by turns, which provide direction change and offset between sequence-adjacent pieces of secondary structure. Tight turns work well as a-a and a-fi joints, but their neatest application is at a hairpin connection... 

Locations of the Asparagine Residues Are Tabulated for p Sheets of at Least Three Strands (and Known Amino Acid Sequence) in the Known Protein Structures ... 

Reva, B. and S. Topiol. 2000. Recognition of protein structure determining the relative energetic contributions of fS-strands, a-helices and loops. Pac Symp Bio-comput 5 165-175. 

Figure 2. Three-dimensional structure of human cytochrome c created by Protein Adviser, ver 3.0 (FQS, Hakata, Japan) with PDB file of human cytochrome c down-loaded from protein structure database of NCBI. a-Helices are shown as purple ribbons, random coils as white strands, and P-tums are blue (see separate colour tip). Heme c is depicted in white straight lines inside the protein.

We encountered the properties of hydrophilic and hydrophobic molecules in our thoughts about driving forces for formation of three-dimensional protein structures. Specifically, proteins fold in a way that puts most of the hydrophobic amino acid side chains into the molecular interior, where they can enjoy each other s company and avoid the dreaded aqueous environment. At the same time, they fold to get the hydrophilic amino acid side chains onto the molecular surface, where they happily interact with that enviromnent. The same ideas are important for the double-stranded helical structure of DNA. The hydrophobic bases are localized within the double hehx, where they interact with each other, and the strongly hydrophilic sugar and phosphate groups are exposed on the exterior of the double helix to the water environment. Now, we need to understand something more about structural features that control these properties. 

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