Helical polypeptide chain structures 3! helix

In summary, we have therefore seen that poly-L-lysine presents a valuable model for a partially helical polypeptide chain, one which is amenable to conformational analysis by optical rotatory dispersion. The method by which residues in a helical conformation may be discerned and counted against a background of disordered regions has been illustrated with this polypeptide under almost ideal conditions. The adequacy of the method is corroborated by copolymers a step closer to proteins in complexity, but some of the limitations that will be encountered in its application to proteins are already foreshadowed. Before this application is discussed, however, two other phenomena relevant to protein structure that are clearly exhibited in synthetic polypeptides, the helix-coil transition and the /3-conformation, will be considered. 

Helically ordered chain structures are not limited to molecules containing a carbon-carbon backbone structure. They also manifest themselves in polypeptides, proteins, and nucleic acids. A very important ordered structure of polypeptides is the alpha-helix deduced by Pauling, Corey, and Branson.(26) In this structure (as contrasted with the extended ordered configuration of a polypeptide chain) the maximum number of hydrogen bonds between the carbonyl oxygen and amino... 

Parvalbumin is a muscle protein with a single polypeptide chain of 109 amino acids. Its function is uncertain, but calcium binding to this protein probably plays a role in muscle relaxation. The helix-loop-helix motif appears three times in this structure, in two of the cases there is a calcium-binding site. Figure 2.13 shows this motif which is called an EF hand because the fifth and sixth helices from the amino terminus in the structure of parvalbumin, which were labeled E and F, are the parts of the structure that were originally used to illustrate calcium binding by this motif. Despite this trivial origin, the name has remained in the literature. 

Figure 3.6 Four-helix bundles frequently occur as domains in a proteins. The arrangement of the a helices is such that adjacent helices in the amino acid sequence are also adjacent in the three-dimensional structure. Some side chains from all four helices are buried in the middle of the bundle, where they form a hydrophobic core, (a) Schematic representation of the path of the polypeptide chain in a four-helrx-bundle domain. Red cylinders are a helices, (b) Schematic view of a projection down the bundle axis. Large circles represent the main chain of the a helices small circles are side chains. Green circles are the buried hydrophobic side chains red circles are side chains that are exposed on the surface of the bundle, which are mainly hydrophilic.

In most four-helix bundle structures, including those shown in Figure 3.7, the a helices are packed against each other according to the "ridges in grooves" model discussed later in this chapter. However, there are also examples where coiled-coil dimers packed by the "knobs in holes" model participate in four-helix bundle structures. A particularly simple illustrative example is the Rop protein, a small RNA-binding protein that is encoded by certain plasmids and is involved in plasmid replication. The monomeric sub unit of Rop is a polypeptide chain of 63 amino acids built up from two... 

Figure 6.25 Schematic diagram of the structure of one dimer of phosphofructokinase. Each polypeptide chain is folded Into two domains (blue and red, and green and brown), each of which has an oi/p structure. Helices are labeled A to M and p strands 1 to 11 from the amino terminus of one polypeptide chain, and respectively from A to M and 1 to 11 for the second polypeptide chain. The binding sites of substrate and effector molecules are schematically marked In gray. The effector site of one subunit is linked to the active site of the other subunit of the dimer through the 6-F loop between helix F and strand 6. (Adapted from T. Schlrmer and P.R. Evans, Nature 343 140-145, 1990.)...

Figure 8.3 The DNA-binding protein Cro from bacteriophage lambda contains 66 amino acid residues that fold into three a helices and three P strands, (a) A plot of the Ca positions of the first 62 residues of the polypeptide chain. The four C-terminal residues are not visible in the electron density map. (b) A schematic diagram of the subunit structure. a helices 2 and 3 that form the helix-turn-helix motif ate colored blue and red, respectively. The view is different from that in (a), [(a) Adapted from W.F. Anderson et al., Nature 290 754-758, 1981. (b) Adapted from D. Ohlendorf et al., /. Mol. Biol. 169 757-769, 1983.]...

The polypeptide chain of the 92 N-terminal residues is folded into five a helices connected by loop regions (Figure 8.6). Again the helices are not packed against each other in the usual way for a-helical structures. Instead, a helices 2 and 3, residues 33-52, form a helix-turn-helix motif with a very similar structure to that found in Cro. 

The L and the M subunits are firmly anchored in the membrane, each by five hydrophobic transmembrane a helices (yellow and red, respectively, in Figure 12.14). The structures of the L and M subunits are quite similar as expected from their sequence similarity they differ only in some of the loop regions. These loops, which connect the membrane-spanning helices, form rather flat hydrophilic regions on either side of the membrane to provide interaction areas with the H subunit (green in Figure 12.14) on the cytoplasmic side and with the cytochrome (blue in Figure 12.14) on the periplasmic side. The H subunit, in addition, has one transmembrane a helix at the car-boxy terminus of its polypeptide chain. The carboxy end of this chain is therefore on the same side of the membrane as the cytochrome. In total, eleven transmembrane a helices attach the L, M, and H subunits to the membrane. 

The phosducin polypeptide chmn, of some 240 amino acids, is folded into two domains (Figure 13.16). The N-terminal domain is mostly a-helical and appears to be quite flexible since only a weak electron density is obtained in the structure determination. The actual path of the polypeptide chain from the end of helix to the beginning of helix Ba is tentative due to slight disorder. This region is close to serine 73 at the beginning of Ba, which also becomes disordered on phosphorylation. 

Collagen, the principal fibrous protein in mammalian tissue, has a tertiary structure made up of twisted a-helices. Three polypeptide chains, each of which is a left-handed helix, are twisted into a right-handed super helix to form an extremely strong tertiary structure. It has remarkable tensile strength, which makes it important in the structure of bones, tendons, teeth, and cartilage. 

The secondary structure of a protein is the shape adopted by the polypeptide chain—in particular, how it coils or forms sheets. The order of the amino acids in the chain controls the secondary structure, because their intermolecular forces hold the chains together. The most common secondary structure in animal proteins is the a helix, a helical conformation of a polypeptide chain held in place by hydrogen bonds between residues (Fig. 19.19). One alternative secondary structure is the P sheet, which is characteristic of the protein that we know as silk. In silk, protein... 

FIGURE 19.19 A representation of part of an a helix, one of the secondary structures adopted by polypeptide chains. The cylinder encloses the "backbone" of the polypeptide chain, and the side groups project outward from it. The thin lines represent the hydrogen bonds that maintain the helical shape. 

Each protein has a unique three-dimensional shape called its tertiary structure. The tertiary structure is the result of the bends and folds that a polypeptide chain adopts to achieve the most stable structure for the protein. As an analogy, consider the cord in Figure 13-39 that connects a computer to its keyboard. The cord can be pulled out so that it is long and straight this corresponds to its primary structure. The cord has a helical region in its center this is its secondary structure. In addition, the helix may be twisted and folded on top of itself This three-dimensional character of the cord is its tertiary structure. 

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... 

It has been suggested that the Sup35p filament may be a bundle of four cylindrical //-sheets or nanotubes (Kishimoto et al., 2004). The nanotube is a hypothetical structure (Perutz et al, 2002) whose winding of the polypeptide chain is topologically similar to that of a //-helix but it is round in cross section and water filled whereas //-helices have cross sections with triangular or other shapes and water is largely excluded from their interiors (Kajava and Steven, 2006). The model of Kishimoto et al. envisaged six coils... 

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