Polyamines Mediate Folding of Primordial Hyperacidic Helical Proteins

Area of Science:

• Biochemistry
• Origin of Life Studies
• Protein Folding

Background:

• Polyamines are known to stabilize nucleic acid structures by neutralizing negative charges.
• The role of polyamines in protein folding, particularly for early or primordial proteins, remains largely unexplored.
• Early proteins may have been acidic due to limited basic amino acid availability in prebiotic conditions.

Purpose of the Study:

• To investigate the potential role of polyamines as chemical chaperones for acidic proteins.
• To explore whether polyamines could have facilitated the folding of early proteins lacking basic residues.
• To compare the folding efficiency of polyamines with simple cations for acidic proteins.

Main Methods:

• Engineered an ancestral protein by replacing all lysines with glutamates, creating a hyperacidic, disordered protein.
• Assessed the folding of this engineered protein in the presence of various polyamines and cations.
• Quantified the potency of polyamines and cations in inducing protein folding at submillimolar concentrations.

Main Results:

• Polyamines efficiently induced folding of the hyperacidic protein at submillimolar concentrations.
• The folding potency of polyamines correlated with the number of amine groups.
• Polyamines were significantly more potent than monovalent cations (Na+) and comparable to divalent cations (Mg2+, Ca2+) at physiological concentrations.

Conclusions:

• Polyamines likely served as crucial chemical chaperones for early proteins lacking basic residues.
• The ability of polyamines to promote folding suggests a role in the origin and early evolution of proteins.
• Coil-helix transitions mediated by polyamines may represent a regulatory mechanism in modern proteins.