Amino acid helix-forming propensity

Early studies on helix propagation had proposed a central residue initiation mechanism, in which helices were believed to form outwards in two directions starting from central residues with high helix-forming propensities. The Chou and Fasman predictions 8,59,60 worked well for predicting centrally located residues with high tendencies to form helices. They, however, did not explain the early observation that certain proteins contain centrally located residues deemed to be helix indifferent or that amino acids with charged side chains seem to occur very frequently at the ends of helices. 

Several factors have to be taken into account for a conclusive interpretation of these results. Recent investigations have shown that some fluorinated amino acids exhibit less favorable helix-forming propensities [31]. Thus, structural perturbations of the helical backbone may contribute to some extent to the general destabilization upon incorporation... 

CO) makes a H-bond with a third amide group away from it. There are 3.6 residues in each turn of the right-handed helix (thus 3.6-fold), and the rise of the helix per turn, the pitch, is —5.4 A. The diameter of the helix backbone is 6 A. Certain amino acids have helix-forming propensities (measured by s values, the helix propagation parameter). They are in the order Ala > Leu > Phe > He > Val > Thr > Gly at internal positions, where Pro is a helix destahilizer (62,63). At N- and C-terminal positions of an a helix, however, Gly shows a substantially increased helix-stabilizing tendency which may be greater than that of Ala (125). 

Initially, we thought there might not be measurable differences in the B-sheet propensities because extended B-sheet structure is much more similar to the unfolded state than the constrained a-helix. Hence, the B-sheet might be merely a "default" structure into which any amino acid may fit, and the Chou-Fasman statistical parameters (12) may therefore result from the strict conformational requirements of a-helices alone. Because B-sheets are more often found fully buried than are a-helices, the statistical distribution of the hydrophobic, B-branched residues in B-sheets may reflect only a hydrophobic requirement rather than a B-sheet forming propensity. 

How does the amino acid sequence of a protein specify its three-dimensional structure How does an unfolded polypeptide chain acquire the form of the native protein These fundamental questions in biochemistry can be approached by first asking a simpler one What determines whether a particular sequence in a protein forms an a helix, a (3 strand, or a turn One source of insight is to examine the frequency of occurrence of particular amino acid residues in these secondary structures (Table 2.3). Residues such as alanine, glutamate, and leucine tend to be present in a helices, whereas valine and isoleucine tend to be present in (3 strands. Glycine, asparagine, and proline have a propensity for being present in turns. 

On one hand, it forms annular p-oligomers with a central channel-like pore that can perforate the plasma membrane of brain cells and affect Ca fluxes. On the other hand, the peptide can form p-rich protofibrils and fibrils. Kallberg et al. studied the propensity of various amyloid proteins to form either a or p secondary structures. They report the interesting observation that all amyloid proteins contain a/p discordant segments. These a/p discordant stretches correspond to a part of the protein that has been shown to adopt an a-helix structure in spite of being composed by amino acids that have a higher propensity... 

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