Simplified protein design biased for prebiotic amino acids yields a foldable, halophilic protein

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 6; pp. 2135 - 2139
• Main Authors: Longo, Liam M., Lee, Jihun, Blaber, Michael
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 05-02-2013; National Acad Sciences
• Subjects: Alphabets; Amino acids; Amino Acids - chemistry; Basic amino acids; Biochemistry; Biological Sciences; Biophysical Phenomena; Biosynthesis; Calorimetry, Differential Scanning; Charge density; Chemical synthesis; Crystallography, X-Ray; Evolution, Molecular; Functional foods & nutraceuticals; Genomes; Halophiles; Models, Molecular; Mutagenesis; Origin of Life; Polypeptides; Prebiotics; Protein Folding; Protein Stability; Proteins; Proteins - chemistry; Proteins - genetics; Salts; Static Electricity
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1219530110

A compendium of different types of abiotic chemical syntheses identifies a consensus set of 10 “prebiotic” α-amino acids. Before the emergence of biosynthetic pathways, this set is the most plausible resource for protein formation (i.e., proteogenesis) within the overall process of abiogenesis. An essential unsolved question regarding this prebiotic set is whether it defines a “foldable set”—that is, does it contain sufficient chemical information to permit cooperatively folding polypeptides? If so, what (if any) characteristic properties might such polypeptides exhibit? To investigate these questions, two “primitive” versions of an extant protein fold (the β-trefoil) were produced by top-down symmetric deconstruction, resulting in a reduced alphabet size of 12 or 13 amino acids and a percentage of prebiotic amino acids approaching 80%. These proteins show a substantial acidification of pI and require high salt concentrations for cooperative folding. The results suggest that the prebiotic amino acids do comprise a foldable set within the halophile environment.