Did Early Functional Proteins Use Metal Ions to Bind ATP?
In early life forms, the first proteins were likely composed of a limited set of amino acid building blocks. Previous work in the Seelig lab has produced random libraries of 85 amino acid-long proteins with ATP binding affinity, made from varying subsets of the 20 modern amino acids. By characterizing these proteins’ binding mechanisms and properties, we hope to gain insight into the nature of early functional proteins. Here, we took initial steps to analyze how the presence of specific metal ions affected the ATP binding of such proteins and what metal ions might be directly bound. Our preliminary data suggest that magnesium and manganese are required for ATP binding for some model primordial proteins composed of just five amino acid types. If confirmed, this would indicate that early proteins exhibited metal preferences akin to those of modern nucleotide-binding proteins. Ongoing work will expand these analyses to additional protein variants, further exploring how metal ion interactions shaped early protein function and drawing comparisons to extant natural proteins.