Polypeptides reverse turns

The reverse turn as a polypeptide conformation in globular proteins. Proc. Natl. Acad. Sci. USA 70 538-542, 1973. 

Richardson-style diagram of the polypeptide backbone of the individual structure of AP-A [46] that is closest to the average over the whole molecule. The locations of the sulfurs in the three disulfide bonds (4-46, 6-36, and 29-47) are shown in CPK format. The locations of reverse turns found in more than half the NMR-derived structures (6-9, 25-28, and 30-33) are indicated by darker backbone shading. 

The regular secondary structures, a helices and /i sheets, are connected by coil or loop regions of various lengths and irregular shapes. A variant of the loop is the f> turn or reverse turn, where the polypeptide chain makes a sharp, hairpin bend, producing an antiparallel / turn in the process. 

Polypeptide Chains Can Change Direetion by Making Reverse Turns and Loops... 

Thioredoxin from E. coli has been studied extensively using biochemical, spectroscopic and X-ray diffraction techniques. The protein consists of a single polypeptide chain of 108 amino acid residues of known sequence. The protein has been cloned and expressed. Thioredoxin of E. coli is a compact molecule with 90% of its residues in hehces, beta-strands or reverse turns. This protein transports electrons via an oxidation-reduction active disulfide". The oxidized form thioredoxin-(S2) is reduced to thioredoxin-(SH)2. In particular, this protein was found to participate in the reduction of ribonucleotides to deoxyribonucleotides. In Fig. 1, the optimized stracture is shown with a carbon backbone for clarity only. The molecule consists of two conformational domains, connected by two helices. The beta-sheet forms the core of the molecule packed on either side by clusters of hydrophobic residues. Helices form the external surface. We used a crystal stracture of the oxidized form of thioredoxin from Escherichia coli that has been refined by the stereochemically restrained least-squares procedure at 1.68 A resolution". ... 

Figure 2.41 Structure of a reverse turn. The CO group of residue i of the polypeptide chain is hydrogen bonded to the NH group of residue i -F3 to stabilize the turn.

In contrast to a-helices, /1-sheets do not involve interactions between amino acids close in sequence. Amino acids that interact within / -sheets are often found widely separated in the primary structure. Therefore, / -sheet formation needs structures that bring two polypeptide segments into close proximity. This is achieved via reverse turn structures [96]. Turns are aperiodic or nonrepetitive elements of secondary structure which mediate the folding of the polypeptide chain into a compact tertiary structure. Turns usually occur on the environment-exposed surface of proteins [97,98], Reverse turns play an important role in polypeptide function, both as elements of structure as well as modulators of bioactivity [99]. Among the reverse turns found in proteins the /1-turn is the most relevant [100]. /1-Turns comprise four amino acid residues (i to i+3) forming an almost complete 180° turn in the direction of the peptide chain [101,102]. 

Proteins take up several different secondary structures, including the a-helix, b-sheet, and reverse turns. The shape of the polypeptide chain is constrained by the planar peptide bond and noncovalent interactions. 

A reverse turn is a region of a polypeptide where the direction changes by about 180°. There are two kinds—those that contain proline and those that do not See Figure 4.6 for examples. 

Polypeptides and proteins can undergo other conformational changes, especially when they exist in relatively compact structures wherein the backbone can fold back on itself, or make a turn (i.e., a site where the polypeptide chain reverses its overall direction). It is these reverse turns (e.g., p-turn or hairpin bend) that afford proteins with globular properties (18). A further discussion of turns is beyond the scope of this chapter, but the interested reader can find many good discussions ofthis topic in other sources (16,19). 

Several of the model cyclic peptides used In these studies were designed to mimic regions of polypeptide chains where hydrogen bonded reverse turns are likely to occur CS., i, Ifl), These peptides contain prollne, an imlno acid which has a high frequency of occurrence in turns (JJ), and which is intrinsically interesting... 

Most proteins have cort5)act, globular shapes, non-regular stmctures requiring reversals in the direction of their polypeptide chains [7]. To make a spherical fold for globular proteins, the residues between regular hehces and strands need to make sharp turns. Turns, reverse turns, or p-tums, were first recognized by Venkatachalam et al [8-10]. 

Helices and pleated sheets account for only about one-half of the structure of the average globular protein. The remaining polypeptide segments have what is called a coil or loop conformation. These nonrepetitive structures are not random they are just more difficult to describe. Globular proteins also have stretches, called reverse turns or j8 bends, where the polypeptide chain abruptly changes direction. These often connect successive strands of /3 sheets and almost always occur at the surface of proteins. 

On average, one third of all residues in proteins are involved in turns that serve to reverse the direction of the polypeptide chain. These turns are an essential feature of globular proteins and are almost always located at the surface. In contrast to a-helices and j8-strands which have repetitive conformational angles, the conformational angles observed in turns occur in sets that are characteristic of each type (Table 11). Turns have been classified according to the commonly observed groups of conformational angles and the number of residues involved. Of these the -hairpin or reverse turn is the most common. This type of turn is frequently used to connect antiparallel y3-strands. 

As emphasized in Chapter 1, examination of protein three-dimensional structures reveals two main characteristics in polypeptide chain folding (1) a hierarchy of organization with different levels of structure, and (2) within each level of structure, a small number of structural patterns are encountered in all globular proteins despite the great number of conformations which may be expected (see Schulz and Schirmer, 1979, and the review in Thomas and Schechter, 1980 Richardson, 1981). At the lower level, secondary structures that commonly occur are essentially right-handed a helix, extended structures, and reverse turns. Then, from interactions between adjacent segments of regular structures, arise only few structural motifs which are found in many proteins (see Fig. 2.9). 

---