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

Huayu Xiong, Brian L. Buckwalter, Hong Ming Shieh, Michael H. Hecht

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Abstract

The tendency of a polypeptide chain to form α-helical or β-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 α-helices or β-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 of the 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 of the amphiphilic peptides is responsible for the observed secondary structures. Thus, for self-assembling 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.

Original languageEnglish (US)
Pages (from-to)6349-6353
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number14
DOIs
StatePublished - Jul 3 1995

All Science Journal Classification (ASJC) codes

  • General

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