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.

Keywords: amyloid; hydrogen bonds; nest; origin of life; peptides; proteins.

Figure 1.

Evolutionary time diagram. (Online version in colour.)

Figure 2.

A simple RL tripeptide nest. Nitrogen atoms are blue, oxygens red, hydrogens white, carbons grey; hydrogen bonds are shown as dashed lines. (a) Only the NH groups. (b) The main chain atoms of the first two residues but only the NH atoms of the third residue. The red spherical atom is the ‘egg’. The ϕ and ψ angles of the first two residues are given by the orange circles in figure 3. (Online version in colour.)

Figure 3.

Ramachandran plot, ϕ versus ψ. (Online version in colour.)

Figure 4.

Trypsin active site nest peptide bound to substrate. Coordinates from the trypsin (above) - pancreatic trypsin inhibitor (below) complex crystal structure PDB code: 2ptc. (Online version in colour.)

Figure 5.

The main chain NH atoms of the P-loop nest peptide bound to the β-phosphate of GDP. Coordinates from GDP-bound P21^ras crystal structure PDB code :5p21. (a) Diagram with hydrogen bonds as dashed lines. (b) Nitrogens blue, phosphorus orange, oxygens red, hydrogens omitted. (Online version in colour.)

Figure 6.

How the LRLR nest residues of P21^ras fit with the sequence.

Figure 7.

Iron–sulfur centres in proteins. (a) The main chain atoms (no hydrogens) are shown as sticks for the nest surrounding the iron–sulfur centre, shown as spheres (iron atoms rust, sulfurs yellow); coordinates from ferredoxin crystal structure PDB code: 2fxn; (b,c) types of iron–sulfur centre. (Online version in colour.)

Figure 8.

Functional peptide nests. (a) Fe₃S₄ in peptide nest and (b) phosphate in peptide nest. (Online version in colour.)

Figure 9.

Potassium channel and selectivity filter. Coordinates are from protein crystal structure PDB code: 1bl8; three potassium atoms in the channel are shown as magenta spheres. Hydrogens and side chains are omitted. (a) One linear peptide from selectivity filter, (b) four peptides of selectivity filter and (c) potassium channel transmembrane domain. (Four colours indicate the four identical subunits. The K⁺ ions indicate the selectivity filter position.) (Online version in colour.)

Figure 10.

Comparison of α-sheet with potassium channel selectivity filter peptide. Side chains are omitted. The α-sheet is modelled. (Online version in colour.)

Figure 11.

α-Sheet. (a,b) α-Sheet partial (δ⁺, δ⁻) charge distribution. (c) Ramachandran plot, as in figure 3, except that the yellow shading shows areas favoured for l-amino acids. (Online version in colour.)

Figure 12.

Haem-like metal peptide. (a) Ni-tetraglycine. (b) Haem. (Online version in colour.)