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Researchers investigated whether short cationic amino acids that were likely abundant in prebiotic conditions (ornithine and 2,4-diaminobutyric acid) could support protein folding, as alternatives to the modern amino acids lysine and arginine which were probably scarce in early Earth. Using computational design and structural analysis, they engineered variants of an ancient protein fold and found that ornithine-containing sequences could fold under concentrated conditions, adopting a double-Z beta-barrel structure that may represent an evolutionary intermediate. This suggests that these simpler cationic amino acids could have enabled primitive protein structures before lysine and arginine were incorporated into the genetic code.
Why it matters
This research provides experimental evidence for how early proteins might have functioned with a different set of amino acids than modern life uses, offering insights into the chemical origins of life and the evolution of the genetic code. Understanding these principles could inform synthetic biology approaches and the design of proteins with non-standard amino acids.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
The evolutionary basis for the selection of the standard proteinogenic amino acids remains elusive, particularly for the long cationic amino acids, lysine and arginine, which were likely scarce in the prebiotic environment. In contrast, shorter cationic amino acids, such as ornithine (Orn), and 2,4-diaminobutyric acid (Dab), are thought to have been more abundant. Here, we investigated whether these prebiotic cationic amino acids can support protein tertiary structure formation, using computational protein design, biophysical and crystallographic analyses, and molecular dynamics (MD) simulations. We designed sequences for an ancient protein fold, the double-{Psi} {beta}-barrel (DPBB), with ornithine and plausible prebiotic amino acid sets. Although all the designed sequences were unfolded under standard dilute aqueous conditions, one Orn-containing variant folded in highly concentrated conditions. Crystallographic analysis revealed that both this peptide and its Dab-substituted derivative adopted the double-Z {beta}-barrel (DZBB) fold, a likely evolutionary intermediate between extant {beta}-barrel folds. Therefore, Orn and Dab might have supported the foldability of primitive proteins before the incorporation of lysine and arginine into the genetic code.
Source: Prebiotic cationic amino acids support formation of an ancient protein fold