Periodicity of polar and nonpolar amino acids is the major determinant of secondary structure in self-assembling oligomeric peptides.

Abstract

The tendency of a polypeptide chain to form ar-helical or ,-strand secondary structure depends upon local and nonlocal effects. Local effects reflect the intrinsic propensities of the amino acid residues for particular secondary structures, while nonlocal effects reflect the positioning of the individual residues in the context of the entire amino acid sequence. In particular, the periodicity of polar and nonpolar residues specifies whether a given sequence is consistent with amphiphilic a-helices or ,8-strands. The importance of intrinsic propensities was compared to that of polar/nonpolar periodicity by a direct competition. Synthetic peptides were designed using residues with intrinsic propensities that favored one or the other type of secondary structure. The polar/nonpolar periodicities of the peptides were designed either to be consistent with the secondary structure favored by the intrinsic propensities of the component residues or in other cases to oppose these intrinsic propensities. Characterization ofthe synthetic peptides demonstrated that in all cases the observed secondary structure correlates with the periodicity of the peptide sequence-even when this secondary structure differs from that predicted from the intrinsic propensities of the component amino acids. The observed secondary structures are concentration dependent, indicating that oligomerization ofthe amphiphilic peptides is responsible for the observed secondary structures. Thus, for selfassembling oligomeric peptides, the polar/nonpolar periodicity can overwhelm the intrinsic propensities of the amino acid residues and serves as the major determinant of peptide secondary structure.The folded structures of proteins are stabilized by a variety of different features, including hydrogen bonding, van der Waals interactions, electrostatic interactions, the hydrophobic effect, and the intrinsic propensities of amino acid side chains for particular secondary structures (1). In recent years, the importance of each of these types of interactions individually has been probed in model peptide systems and in mutagenically altered proteins (2-15). The importance of one type of interaction relative to another type of interaction has received far less attention. This is not surprising since natural proteins typically are stabilized by the concerted action of numerous interrelated features, and it is not possible to isolate any one of these features from all the others. The study of proteins, however, is no longer limited to natural proteins. It is now possible to construct proteins that are designed entirely de novo (16)(17)(18)(19)(20). With the ability to design proteins from first principles comes the possibility to design structures by focusing on one type of interaction with the hope that optimizing this type will compensate for the mistakes that may result from an incomplete understanding of other features. Thus, the emerging field of de novo proteinThe publication costs of this article were defrayed in part by page charge payment. This art...

Q455V mutation in COL8A2 is associated with Fuchs' corneal dystrophy in Korean patients

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Conversion of a β‐strand to anα‐helix induced by a single‐site mutation observed in the crystal structure of fis mutant pro26Ala

“…The peptide of '"DQVTQKA2' is located at the edge of the Fis molecule and is highly exposed to solvent; therefore, the tertiary context influence to direct a P-sheet structure is reduced. Third, this peptide does not contain strong periodicity of polar and nonpolar amino acids of 3.6 residues for a-helices or 2 residues for P-sheets (Xiong et al, 1995). The combination of the second and third factors should result in a peptide that is more flexible and more capable of adopting different secondary structures.…”

Foldamer hypothesis for the growth and sequence differentiation of prebiotic polymers

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