Protein three-dimensional structures at the origin of life

Abstract

Proteins are relatively easy to synthesize, compared to nucleic acids and it is likely that there existed a stage prior to the RNA world which can be called the protein world. Some of the three-dimensional (3D) peptide structures in these proteins have, we argue, been conserved since then and may constitute the oldest biological relics in existence. We focus on 3D peptide motifs consisting of up to eight or so amino acid residues. The best known of these is the ‘nest’, a three- to seven-residue protein motif, which has the function of binding anionic atoms or groups of atoms. Ten per cent of amino acids in typical proteins belong to a nest, so it is a common motif. A five-residue nest is found as part of the well-known P-loop that is a recurring feature of many ATP or GTP-binding proteins and it has the function of binding the phosphate part of these ligands. A synthetic hexapeptide, ser–gly–ala–gly–lys–thr, designed to resemble the P-loop, has been shown to bind inorganic phosphate. Another type of nest binds iron–sulfur centres. A range of other simple motifs occur with various intriguing 3D structures; others bind cations or form channels that transport potassium ions; other peptides form catalytically active haem-like or sheet structures with certain transition metals. Amyloid peptides are also discussed. It now seems that the earliest polypeptides were far from being functionless stretches, and had many of the properties, both binding and catalytic, that might be expected to encourage and stabilize simple life forms in the hydrothermal vents of ocean depths.