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Nature disfavors sequences of alternating polar and non-polar amino acids: implications for amyloidogenesis1

https://doi.org/10.1006/jmbi.2000.3514Get rights and content

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.

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Acknowledgements

We thank Michael West, Laura Landweber and Tzachi Pilpel for comments on the manuscript. This work was supported by the Culpepper Foundation, the Biological Sciences Program of the ARO, the New Jersey Center for Biomaterials, and NSF MRSEC (DMR98-09483).

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1

Edited by F. E. Cohen

2

Present address: B. M. Broome, UCLA School of Medicine, Los Angeles, CA, USA.

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