Amino acid sequence ordered/disordered proteins

Coacervation occurs in tropoelastin solutions and is a precursor event in the assembly of elastin nanofibrils [42]. This phenomenon is thought to be mainly due to the interaction between hydro-phobic domains of tropoelastin. In scanning electron microscopy (SEM) picmres, nanofibril stmc-tures are visible in coacervate solutions of elastin-based peptides [37,43]. Indeed, Wright et al. [44] describe the self-association characteristics of multidomain proteins containing near-identical peptide repeat motifs. They suggest that this form of self-assembly occurs via specific intermolecular association, based on the repetition of identical or near-identical amino acid sequences. This specificity is consistent with the principle that ordered molecular assembhes are usually more stable than disordered ones, and with the idea that native-like interactions may be generally more favorable than nonnative ones in protein aggregates. 

Intrinsic disorder might not be encoded by the sequence, but rather might be the result of the absence of suitable tertiary interactions. If this were the general cause of intrinsic disorder, any subset of ordered sequences and any subset of disordered sequences would likely be the same within the statistical uncertainty of the sampling. On the other hand, if intrinsic disorder were encoded by the amino acid sequence, any subset of disordered sequences would likely differ significantly from samples of ordered protein sequences. Thus, to test the hypothesis that disorder is encoded by the sequence, we collected examples of intrinsically ordered and intrinsically disordered proteins, then determined whether and how their sequences were distinguishable. 

The enrichments and depletions displayed in Figure 1 are concordant with what would be expected if disorder were encoded by the sequence (Williams et al., 2001). Disordered regions are depleted in the hydrophobic amino acids, which tend to be buried, and enriched in the hydrophilic amino acids, which tend to be exposed. Such sequences would be expected to lack the ability to form the hydrophobic cores that stabilize ordered protein structure. Thus, these data strongly support the conjecture that intrinsic disorder is encoded by local amino acid sequence information, and not by a more complex code involving, for example, lack of suitable tertiary interactions. 

The results described in Section I suggest that amino acid sequence codes for intrinsic protein disorder. In this circumstance, constructing a predictor of order and disorder would be useful as a means to extend and generalize from the current experimental results. 

When the number of amino acids in a polypeptide chain reaches more than fifty, a protein exists. The structure of both polypeptides and proteins dictate how these biomolecules function. There are several levels of structure associated with polypeptides and proteins. The sequence of the amino acids forming the backbone of the protein is referred to as the primary structure. A different order or even a minor change in an amino acid sequence creates an entirely different molecule. Just reversing the order of amino acids in a dipeptide changes how the dipeptide functions. An example of this is sickle-cell anemia. Sickle-cell anemia is a genetic disorder that occurs when the amino acid valine replaces... 

Once sufficient numbers of intrinsically disordered and ordered protein sequences were collected, it became possible to compare them directly. The sequences in these databases were examined for dilferences in amino acid composition, sequence attributes, and evolutionary characteristics. 

Ellipsoidal and spherical shape are especially prevalent among proteins, which are naturally occurring copolymers of a-amino acids. Certain sequences of these a-amino acids are helical, whereas others are not (Figure 4-14). The interaction of these ordered and disordered conformational sequences with each other and with the solvent thus determine the internal structure and external shape. In water, for example, hydrophilic groups will tend to occupy positions on the surface of the protein, and hydrophobic groups will tend towards the interior. With myoglobin, for example, only two amino acid residues with hydrophilic substituents are to be encountered in the protein interior. Such a protein molecule, then, will appear as a quite compact sphere or as an ellipsoid. 

In general, it is expected that most peptides composed of mixtures of polar and nonpolar residues adopt amphiphilic, interfacially active structures. Whether these structures are ordered or not depends on the sequence of amino acids. In contrast, nonpolar peptides are expected to partition from water to a nonpolar medium. Since they are disordered in the aqueous solution but, most likely, exist as a-helices in a nonpolar environment, they must fold before they reach thermodynamic equilibrium in this environment, presumably during the transfer across the interface. This is clearly relevant to the insertion and formation of transmembrane helices and the translocation of proteins across the membrane initiated by signal sequences. 

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