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.

Origin of Life: The Point of No Return

“…Theoretically, RNA self-replicating ribozymes could trigger Darwinian evolution when information and structure/function are carried out by the same RNA, but the natural formation of this type of ribozyme is highly unlikely as we will discuss later. Another hypothesis describes peptides as the first important entities for the origin of life, before RNA or DNA, and the code formation [28][29][30][31]. The peptide-first type of hypothesis faces the same problem for initiating Darwinian evolution as was described for the metabolism-first or lipids-first suggestions.…”

“…The peptide-first type of hypothesis faces the same problem for initiating Darwinian evolution as was described for the metabolism-first or lipids-first suggestions. Without a doubt, short peptides could be directly synthesized in most of the proposed prebiotic scenarios and some amino acid combinations would have a significant functional impact [28][29][30][31]. Despite this possibility, if the peptides are not coded, Darwinian evolution cannot exist and the system will not advance toward longer functional peptides, i.e., the formation of functional peptides would occur with the same probability as those that were initially synthesized.…”

Cofactors as Molecular Fossils To Trace the Origin and Evolution of Proteins

“…ABC transporters can bind ATP, [59] and P‐loop NTPases can bind ATP and GTP [60] . A synthetic hexapeptide mimicking the simplest P‐loop sequence was found to bind inorganic phosphate through hydrogen bonds between the main‐chain NH atoms and the phosphate O atoms, which implies a primitive interaction mechanism for proteins and such cofactors [61,62] . This phosphate‐dependent mechanism is common in protein‐cofactor interactions.…”

Quantifying Mineral-Ligand Structural Similarities: Bridging the Geological World of Minerals with the Biological World of Enzymes

“…Mineral compounds have been highlighted as candidate materials for catalysis [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ], information storage [ 12 , 13 , 14 ], and compartmentalization, concentration and polymerization [ 5 , 11 , 15 , 16 , 17 ], among others [ 4 , 5 , 13 , 18 ]. Focusing on catalysis, many authors have highlighted the compelling structural similarities between key inorganic enzyme clusters, and minerals [ 7 , 8 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Iron-sulfur clusters are employed across a vast range of essential biochemical functions [ 27 , 28 ].…”