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 language | English (US) |
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Pages (from-to) | 961-968 |
Number of pages | 8 |
Journal | Journal of Molecular Biology |
Volume | 296 |
Issue number | 4 |
DOIs | |
State | Published - Mar 3 2000 |
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Structural Biology
Keywords
- Amyloid
- Binary patterning
- Fibril
- Protein aggregation
- Protein design