Protein structure coil conformation

A prior distribution for sequence profiles can be derived from mixtures of Dirichlet distributions [16,51-54]. The idea is simple Each position in a multiple alignment represents one of a limited number of possible distributions that reflect the important physical forces that determine protein structure and function. In certain core positions, we expect to get a distribution restricted to Val, He, Met, and Leu. Other core positions may include these amino acids plus the large hydrophobic aromatic amino acids Phe and Trp. There will also be positions that are completely conserved, including catalytic residues (often Lys, GIu, Asp, Arg, Ser, and other polar amino acids) and Gly and Pro residues that are important in achieving certain backbone conformations in coil regions. Cys residues that form disulfide bonds or coordinate metal ions are also usually well conserved. 

Proteins fold on a time scale from [is to s. Starting from a random coil conformation, proteins can find their stable fold quickly although the number of possible conformations is astronomically high. The protein folding problem is to predict the folding and the final structure of a protein solely from its sequence. 

Fig. 44. Distribution of Ala in the Ramachandran plot when using (A) all secondary structure conformations in the protein database or (B) only those Ala residues in a coil conformation. (From Serrano, 1995. 1995, with permission from Academic Press.)...

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. 

Before doing so, we briefly examine the influence of conformation and flexibility. Indeed, formation of succinimide is limited in proteins due to conformational constraints, such that the optimal value of the and ip angles (Sect. 6.1.2) around the aspartic acid and asparagine residues should be +120° and -120°, respectively [99], These constraints often interfere with the reactivity of aspartic acid residues in proteins, but they can be alleviated to some extent by local backbone flexibility when it allows the reacting groups to approach each other and, so, favors the intramolecular reactions depicted in Fig. 6.27. When compared to the same sequence in more-flexible random coils, elements of well-formed secondary structure, especially a-helices and 13-turns, markedly reduce the rate of succinimide formation and other intramolecular reactions [90][100],... 

Independently, Ruan etal. (1990) demonstrated that unnatural metal-ligating residues may likewise be utilized toward the stabilization of short a helices by transition metal ions (including Zn " ")—these investigators reported that an 11-mer is converted from the random coil conformation to about 80% a helix by the addition of Cd at 4°C. These results suggest that the engineering of zinc-binding sites in small peptides or large proteins may be a powerful approach toward the stabilization of protein secondary structure. 

Approximately one half of an average globular protein is organized into repetitive structures, such as the a-helix and/or 3-sheet. The remainder of the polypeptide chain is described as having a loop or coil conformation. These nonrepetitive secondary structures are not... 

As a prelude to discussing the mechanism of folding of intact proteins in the next chapter, we end this one with a discussion of the kinetics and mechanism of folding of isolated secondary structural elements of proteins from the random coil conformation. 

Calsequestrin is a calcium-storage protein found in the sacroplasmic reticulum, which binds about 50 calcium ions per monomer (molecular weight 40 000) with binding constants in the range 103-105 dm3 mol. Release and uptake of Ca2+ during muscle contradion and relaxation involve this store. Calsequestrin from rabbit skeletal muscle has a random coil conformation in the absence of calcium. Binding of Ca2+ is associated with a change to a more compact structure.267... 

Polypeptides and poly(a-amino acid)s have a quite unique position amongst synthetic polymers. The reason for this is that most common synthetic polymers have very little long range order in solution and their properties are the products of statistical random coil conformations. Polypeptides, in contrast, can adopt well defined, ordered structures typical of those existing in proteins, such as a-helix and P-struc-tures. Moreover, the ordered structures can undergo conformational changes to the random coil state as cooperative transitions, analogous to the denaturation of proteins. 

The four protein conformations that provide mechanical stability to cells, tissues, and organs include the random coil or amorphous structure that characterizes a part of the structure of elastin, the a helix, which is represented by the keratin molecule, the collagen triple helix, and the p structure of silk. In humans the P structure is found only in short sequences connecting parts of other structures such as the a helix, but serves as an example of the relationship between protein structure and properties. The ultimate tensile strength and modulus of each structure differs as discussed below. 

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