Protein structure helices

B. Secondary Protein Structure - Helices and Pleated Sheets... 

The cooperative effects in secondary protein structures, helix and sheet have been reported [53]. The linear chain of formamide which resembles peptides has large cooperativity in H-bond, which is 2.5 times that of formamide dimer. For the parallel and antiparallel sheet in secondary protein structures, there was no cooperativity in the parallel direction, while significant cooperativity exists in perpendicular direction. In methanol solvent system, the cooperative effects were reduced, indicating that the cooperativity is due to the polarization effect. 

The most common location for an a helix in a protein structure is along the outside of the protein, with one side of the helix facing the solution and the other side facing the hydrophobic interior of the protein. Therefore, with 3.6 residues per turn, there is a tendency for side chains to change from hydrophobic to hydrophilic with a periodicity of three to four residues. Although this trend can sometimes be seen in the amino acid sequence, it is not strong enough for reliable stmctural prediction by itself, because residues that face the solution can be hydrophobic and, furthermore, a helices can be either completely buried within the protein or completely exposed. Table 2.1 shows examples of the amino acid sequences of a totally buried, a partially buried, and a completely exposed a helix. 

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.

In the first edition of this book this chapter was entitled "Antiparallel Beta Structures" but we have had to change this because an entirely unexpected structure, the p helix, was discovered in 1993. The p helix, which is not related to the numerous antiparallel p structures discussed so far, was first seen in the bacterial enzyme pectate lyase, the stmcture of which was determined by the group of Frances Jurnak at the University of California, Riverside. Subsequently several other protein structures have been found to contain p helices, including extracellular bacterial proteinases and the bacteriophage P22 tailspike protein. 

The coiled-coil structure of the leucine zipper motif is not the only way that homodimers and heterodimers of transcription factors are formed. As we saw in Chapter 3 when discussing the RNA-binding protein ROP, the formation of a four-helix bundle structure is also a way to achieve dimerization, and the helix-loop-helix (HLH) family of transcription factors dimerize in this manner. In these proteins, the helix-loop-helix region is preceded by a sequence of basic amino acids that provide the DNA-binding site (Figure 10.23), and... 

Phillips, S.E.V. Built by association structure and function of helix-loop-helix DNA-binding proteins. Structure 2 1-4, 1994. 

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. 

As described in Chapter 2, the first complete protein structure to be determined was the globular protein myoglobin. However, the a helix that was recognized in this structure, and which has emerged as a persistent structural motif in the many hundreds of globular proteins determined subsequently, was first observed in x-ray diffraction studies of fibrous proteins. 

In globular protein structures, it is common for one face of an a-helix to be exposed to the water solvent, with the other face toward the hydrophobic interior of the protein. The outward face of such an amphiphilic helix consists mainly of polar and charged residues, whereas the inward face contains mostly nonpolar, hydrophobic residues. A good example of such a surface helix is that of residues 153 to 166 of flavodoxin from Anabaena (Figure 6.24). Note that the helical wheel presentation of this helix readily shows that one face contains four hydrophobic residues and that the other is almost entirely polar and charged. 

Two of the most common motifs in the hundreds of known protein structures are the so-called a helix and the P sheet. 

These are exciting times for peptide based materials. The number of investigators in this field and consequently the number of publications in this area have increased tremendously in recent years. Not since the middle of the past century has there been so much activity focused on the physical properties of peptidic materials. Then, efforts were focused on determination of the fundamental elements that make up protein structures, leading to the discoveries of the a—helix and the (3-sheet. Many years of study followed where the propensities of individual and combinations of amino acids to adopt and stabilize these structures were investigated. Now, this knowledge is being applied to the preparation, assembly, and use of peptide based materials with designed sequences. This volume summarizes recent developments in all these areas. 

Although other secondary protein structures play roles in determining the shapes of proteins, the helix and pleated sheet occur most frequently. A discussion of less common secondary structures is beyond the scope of this text. 

The essential distinction between the approaches used to formulate and evaluate proteins, compared with conventional low molecular weight drugs, lies in the need to maintain several levels of protein structure and the unique chemical and physical properties that these higher-order structures convey. Proteins are condensation polymers of amino acids, joined by peptide bonds. The levels of protein architecture are typically described in terms of the four orders of structure [23,24] depicted in Fig. 2. The primary structure refers to the sequence of amino acids and the location of any disulfide bonds. Secondary structure is derived from the steric relations of amino acid residues that are close to one another. The alpha-helix and beta-pleated sheet are examples of periodic secondary structure. Tertiary... 

Fig. 2 Illustration of protein structure levels. Shown are primary structure (amino acid sequence), secondary structure (local order of protein chain, a-helix shown as an example), tertiary structure (assembly of secondary structure elements), and quaternary structure (relationship of different protein chain in multisubunit protein). (From Ref. 66.)...

The N-terminal domain of the OCP is an orthogonal alpha-helical bundle, subdivided into two four-helix bundles (Figure 1.3a and c). These subdomains are composed of discontinuous segments of the polypeptide chain (gray and white in Figure 1.3c). To date, the OCP N-terminal domain is the only known protein structure with this particular fold (Pfam 09150). The hydroxyl terminus of the 3 -hydroxyechinenone is nestled between the two bundles. The C-terminal domain (dark... 

A model of a Pn helix formed by alanine side chains is illustrated for reference in Figure 13B (see color insert), while Figure 13A illustrates the common occurrence of the Pn backbone conformation among residues outside regions of regular secondary structure (Kleywegt and Jones, 1996 Serrano, 1995 Stapley and Creamer, 1999) in protein structures from the Protein Data Bank. 

The PPII conformation is abundant in known protein structures, although PPII helices are not particularly common. Sreerama and Woody (1994) found that around 10% of all protein residues are in the PPII helical conformation. However, the majority of those are not part of a PPII helix. Stapley and Creamer (1999) and Adzhubei and Sternberg (1993) found that only 2% of the residues in the proteins examined were part of PPII helices four residues or longer in length. Moreover, on average, each protein possesses just one such PPII helix. The PPII helices found tend to be very short. Stapley and Creamer (1999) found that 95% of the PPII helices in their protein data set were only four, five, or six residues long. 

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