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Functional rapidly folding proteins from simplified amino acid sequences

Nature Structural Biology volume 4, pages 805–809 (1997)Cite this article

Abstract

Early protein synthesis is thought to have involved a reduced amino acid alphabet. What is the minimum number of amino acids that would have been needed to encode complex protein folds similar to those found in nature today? Here we show that a small β-sheet protein, the SH3 domain, can be largely encoded by a five letter amino acid alphabet but not by a three letter alphabet. Furthermore, despite the dramatic changes in sequence, the folding rates of the reduced alphabet proteins are very close to that of the naturally occurring SH3 domain. This finding suggests that despite the vast size of the search space, the rapid folding of biological sequences to their native states is not the result of extensive evolutionary optimization. Instead, the results support the idea that the interactions which stabilize the native state induce a funnel shape to the free energy landscape sufficient to guide the folding polypeptide chain to the proper structure.

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Authors and Affiliations

  1. Department of Biochemistry, University of Washington, Seattle, Washington, 98195, USA

    David S. Riddle, Jed V. Santiago, Susan T. Bray-Hall, Nikunj Doshi, Viara P. Grantcharova, Qian Yi & David Baker

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  1. David S. Riddle
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Riddle, D., Santiago, J., Bray-Hall, S. et al. Functional rapidly folding proteins from simplified amino acid sequences. Nat Struct Mol Biol 4, 805–809 (1997). https://doi.org/10.1038/nsb1097-805

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