Nature disfavors sequences of alternating polar and non-polar amino acids: Implications for amyloidogenesis

Bede M. Broome, Michael H. Hecht

Research output: Contribution to journalArticle

140 Scopus citations

Abstract

Recent experiments with combinatorial libraries of de novo proteins have demonstrated that sequences designed to contain polar and non-polar amino acid residues arranged in an alternating pattern form fibrillar structures resembling β-amyloid. This finding prompted us to probe the distribution of alternating patterns in the sequences of natural proteins. Analysis of a database of 250,514 protein sequences (79,708,024 residues) for all possible binary patterns of polar and non-polar amino acid residues revealed that alternating patterns occur significantly less often than other patterns with similar compositions. The under-representation of alternating binary patterns in natural protein sequences, coupled with the observation that such patterns promote amyloid-like structures in de novo proteins, suggests that sequences of alternating polar and non-polar amino acids are inherently amyloidogenic and consequently have been disfavored by evolutionary selection. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)961-968
Number of pages8
JournalJournal of Molecular Biology
Volume296
Issue number4
DOIs
StatePublished - Mar 3 2000

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Keywords

  • Amyloid
  • Binary patterning
  • Fibril
  • Protein aggregation
  • Protein design

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