Protein structure tight turns

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... 

Our next examples concern the characterization of /J-turns, which are structural elements that permit polypeptide chain reversals in proteins [65]. Tight turns in proteins and peptides, involving two residues as folding nuclei, have been widely investigated [66-69]. We have applied our GA technique for structure solution of the peptides Piv-LPro-Gly-NHMe and Piv-LPro-y-Abu-NHMe from powder diffraction data, in order to explore the structural properties of these materials (particularly with regard to the formation of /J-turns). 

The immunoglobulin structure in Figure 6.45 represents the confluence of all the details of protein structure that have been thus far discussed. As for all proteins, the primary structure determines other aspects of structure. There are numerous elements of secondary structure, including /3-sheets and tight turns. The tertiary structure consists of 12 distinct domains, and the protein adopts a heterotetrameric quaternary structure. To make matters more interesting, both intrasubunit and intersubunit disulfide linkages act to stabilize the discrete domains and to stabilize the tetramer itself. 

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. 

One additional sort of tight turn involving only three residues has been described theoretically (Nemethy and Printz, 1972) and also observed at least once in a protein structure (Matthews, 1972). This is the y turn, which has a very tight hydrogen bond across a seven-atom ring between the CO of the first residue and the NH of the third (see Fig. 34b). It also can continue with a normal /3 sheet hydrogen bond between the NH of residue 1 and the CO of residue 3. Residues 1 and 3 are not far from the usual /3 conformation, while 2 = 70° and th = - 60°. 

To form a globular protein, a polypeptide chain must repeatedly fold back on itself. The turns or bends by which this is accomplished can be regarded as a third major secondary structural element in proteins. Turns often have precise structures, a few of which are illustrated in Fig. 2-24. As components of the loops of polypeptide chains in active sites, turns have a special importance for the functioning of enzymes and other proteins. In addition, tight turns are often sites for modification of proteins after their initial synthesis (Section F). 

Figure 4.9 Two major types of ft (tight) turns. In type II, R3 is usually glycine. (Reproduced with permission from Richardson JS. The anatomy and taxonomy of protein structure. Adv Prot Chem 34 167-339, 1981.)...

Interestingly, it appears that it is easier to induce the formation of a helical hairpin with the tight turn on the lumenal side of the ER membrane than one with the opposite orientation (cytoplasmic turn) i.e., whereas a single Pro is enough to convert the 40-residues long poly (Leu) stretch to a helical hairpin with a lumenal turn, three consecutive prolines are needed for a helical hairpin with a cytoplasmic turn to form (Saaf et al., 2000) (Fig. 2B). If one only considers simple protein—lipid interactions there is no obvious thermodynamic reason why this should be so instead, we favor the view that this reflects a constraint on helical hairpin structure imposed by the Sec machinery. 

GcL contains 544 amino acids in a single chain folded into one domain, making it one of the largest structural domains observed to date in a protein. Like RmL, GcL is an a structure with a central, predominantly parallel jS sheet. There are 11 strands in the central sheet, 3 more in a small additional sheet, and 17 a helices (Fig. 2). The catalytic Ser-217, a part of the G-X-S-X-G pentapeptide, is located at a tight turn between the C terminus of a /3 strand and an N terminus of an a helix, exactly as observed in RmL. The hydroxyl of Ser-217 is hydrogen bonded to the imidazole of His-463, which in turn donates a hydrogen bond to Glu-354. Thus, GcL constitutes the first known example of a serine hydrolase in which the acid residue of the triad is a glutamate and not an aspartate. 

To perform activities, the protein units need a definite and stable 3D structure. When a protein folds to form a well-defined 3D structure, it exhibits primary, secondary, tertiary, and quaternary levels of structures. The genetically determined sequence of amino acids is the primary structure. The primary structure is often modeled as beads on a string, where each bead represents one amino acid unit. The intermediate level of protein structure is called secondary structure. This includes the a-heUces, -sheets, and turns that allow the amides to hydrogen bond very efhciently with one another. The tertiary structure might be modeled as a tightly packed snowball to form the well-defined 3D structure, where each atom in the protein has a well-defined... 

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