Back in time to the Gly-rich prototype of the phosphate binding elementary function

Area of Science:

• Biochemistry and Molecular Evolution
• Origin of Life studies

Background:

• Nucleotide binding is a fundamental biological process with ancient origins.
• Phosphate binding is a critical component in the function of nucleotide-containing ligands.
• Prebiotic evolution laid the groundwork for essential molecular functions.

Purpose of the Study:

• To review and analyze the structural, functional, and evolutionary aspects of phosphate binding.
• To computationally reconstruct the most ancient sequence prototype for phosphate binding.
• To identify and characterize key phosphate-binding signatures.

Main Methods:

• Literature review of prebiotic evolution and phosphate binding.
• Computational experiment to reconstruct ancient sequence prototypes.
• Derivation of position-specific scoring matrices (PSSMs) for phosphate-binding signatures.
• Analysis of evolutionary connections between signatures.

Main Results:

• Two major phosphate-binding signatures, GxGxxG and GxxGxG, were identified, discriminating between nucleotide and dinucleotide ligands.
• The dinucleotide-associated signature (GxGxxG) appears more generic and can bind nucleotide phosphates.
• The reconstructed prototype signature, GxGGxG, highlights the role of glycine in phosphate binding flexibility and interaction.

Conclusions:

• The study elucidates the ancient evolutionary history of phosphate binding.
• Reconstructed prototypes reveal the fundamental amino acid requirements for early molecular recognition.
• Glycine, valine, and alanine residues were integral to the versatility and diversification of phosphate-binding functions.