title: Nature disfavors sequences of alternating polar and non-polar amino acids: implications for amyloidogenesis.
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 beta-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.
authors.affiliation: Department of Chemistry, Princeton University, Princeton, NJ, 08544-1009, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Broome
authors.forename: M H
authors.initials: MH
authors.lastname: Hecht
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000682:Amyloid / Q000737:chemistry*; D000686:Amyloidosis / Q000378:metabolism*; D016208:Databases, Factual; D006801:Humans; D015202:Protein Engineering
chemical_list: D000596:Amino Acids; D000682:Amyloid