Protein structure turns

Figure 4 Sample spatial restraint m Modeller. A restraint on a given C -C , distance, d, is expressed as a conditional probability density function that depends on two other equivalent distances (d = 17.0 and d" = 23.5) p(dld, d"). The restraint (continuous line) is obtained by least-squares fitting a sum of two Gaussian functions to the histogram, which in turn is derived from many triple alignments of protein structures. In practice, more complicated restraints are used that depend on additional information such as similarity between the proteins, solvent accessibility, and distance from a gap m the alignment.

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. 

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. 

Because of this length dependence, IR and VCD of -turns may provide a means of discriminating and detecting them in a protein structure. Short Aib peptide results provide examples of type III /3-turn VCD (Yasui et al., 1986b), while cyclic peptides have been used to study type I and II turns, which are implied to have unique VCD band shapes (Wyssbrod and Diem, 1992 Xie et al., 1995). We have identified distinct turn modes... 

When one of the Fe-coordinating Ns of the porphyrin is made inequivalent to the others, for example, by pulling on it, or by putting a protein structure around the cofactor, then the molecular x axis and y axis become inequivalent, and the axial EPR spectrum turns into the rhombic spectrum in trace d with derivative trace e (see also Table 5.4). There are now three features in the spectrum a peak, a zero crossing, and a negative peak, and their field positions closely (exactly for zero linewidth) correspond to those of the g-values, gx, gy, and gz. Finally, in trace f of Figure 5.4, which is the experimental X-band spectrum of cytochrome c, it can be seen that not only the g-value (peak position) but also the linewidth is frequently found to be anisotropic. This extra complication will be discussed extensively in Chapter 9. 

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. 

In principle, a de novo protein structure determination requires one round of 7 Candid cycles. This is realistic for projects where an essentially complete chemical shift list is available and much effort was made to prepare a complete high-quality input of NOESY peak lists. In practice, it turned out to be more efficient to start a first round of Candid analysis without excessive work for the preparation of the input peak list, using an slightly incomplete list of safely identifiable NOESY cross peaks, and then to use the result of the first round of Candid assignment and structure determination as additional information from which to prepare an improved, more complete NOESY peak list as input for a second round of 7 Candid cycles. 

In order to evaluate the occurrence and distinctness of the major turn types as found empirically in protein structures, Figs. 35 through... 

Fig. 32. Stereo drawings of particular examples of types II (a) and II (b) turns from the known protein structures, (a) Concanavalin A 43-46 (Gln-Asp-Gly-Lys) (b) car-boxypeptidase A 277-280 (Tyr-Gly-Phe-Leu).

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°. 

By any sort of definition, turns are an important feature of protein structure. Kuntz (1972) found 45% of protein backbone in turns or loops Chou and Fasman (1977) found 32% of protein chain in turns (counting four residues per turn) and Zimmerman and Scheraga (1977b) found 24% of the nonhelical residues in turns (counting only the central dipeptide). There are also some particular proteins whose structure appears heavily dependent on turns Fig. 38 shows high-potential iron protein (Carter et ah, 1974), with the 17 turns in 85 residues indicated and their location at the surface evident. 

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... 

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