Simplified Protein Design Biased for Prebiotic Amino Acids Yields A
Simplified protein design biased for prebiotic amino acids yields a foldable, halophilic protein Liam M. Longo, Jihun Lee1, and Michael Blaber2 Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306-4300 Edited by Brian W. Matthews, University of Oregon, Eugene, OR, and approved December 19, 2012 (received for review November 9, 2012) A compendium of different types of abiotic chemical syntheses reducing the potential diversity of interactions that can be encoded identifies a consensus set of 10 “prebiotic” α-amino acids. Before the to that of currently proposed theoretic limits for foldability (14– emergence of biosynthetic pathways, this set is the most plausible 16) (thus, to be able to support protein foldability, the 10 pre- resource for protein formation (i.e., proteogenesis) within the overall biotic amino acids would need to be a remarkably efficient selec- process of abiogenesis. An essential unsolved question regarding tion); (ii) aromatic residues, key contributors to extensive van der this prebiotic set is whether it defines a “foldable set”—that is, does Waals interactions in hydrophobic cores that serve as a driving force it contain sufficient chemical information to permit cooperatively for protein collapse, are absent in the prebiotic alphabet; and (iii) folding polypeptides? If so, what (if any) characteristic properties there are no basic amino acids in the prebiotic set, thus restricting might such polypeptides exhibit? To investigate these questions, protein design to acidic polypeptides, limiting the presence of salt two “primitive” versions of an extant protein fold (the β-trefoil) were bridge interactions and resulting in acidic pI (1, 3). produced by top-down symmetric deconstruction, resulting in a re- To date, there has been no experimental demonstration that the duced alphabet size of 12 or 13 amino acids and a percentage of prebiotic set of amino acids comprises a foldable set; additionally, prebiotic amino acids approaching 80%.
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