Amino acid sequences disorders

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. 

II. Prediction of Order and Disorder from the Amino Acid Sequence. 37... 

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 success rate of every prediction set was greater than the value of 50% expected by chance. Specifically, the various sets of predictions differed from the 50% value by about 3 standard deviations (for the lowest success rate, which was for the merged data) to about 12 standard deviations (for the highest success rates, which were for the medium and long regions of disorder). Overall, these data provided very strong support for our hypothesis that disorder is encoded by the amino acid sequence (Romero et al., 1997b). 

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... 

Although it has been known for two decades that the three-dimensional structure of a protein is determined by its amino acid sequence, the forces that drive a disordered polypeptide chain into its final, folded conformation, and once there maintain this compact structure are only understood in general terms. There are two broad classes of noncovalent interactions... 

Thalassemias and hemoglobinopathies are clinical disorders related to Hb pathophysiology. Regarding the former, inadequate production of a- or j3-globin chains results in a- or P-thalassemia, respectively. Modifications in the amino acid sequence of either the a- or 3-chains results in hemoglobinopathies. 

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