Frozen in Time: The History of Proteins

Abstract

The ribosome is imprinted with a detailed molecular chronology of the origins and early evolution of proteins. Here we show that when arranged by evolutionary phase of ribosomal evolution, ribosomal protein (rProtein) segments reveal an atomic level history of protein folding. The data support a model in which aboriginal oligomers evolved into globular proteins in a hierarchical step-wise process. Complexity of assembly and folding of polypeptide increased incrementally in concert with expansion of rRNA. (i) Short random coil proto-peptides bound to rRNA, and (ii) lengthened over time and coalesced into β-β secondary elements. These secondary elements (iii) accreted and collapsed, primarily into β-domains. Domains (iv) accumulated and gained complex super-secondary structures composed of mixtures of α-helices and β-strands. Early protein evolution was guided and accelerated by interactions with rRNA. rRNA and proto-peptide provided mutual protection from chemical degradation and disassembly. rRNA stabilized polypeptide assemblies, which evolved in a stepwise process into globular domains, bypassing the immense space of random unproductive sequences. Coded proteins originated as oligomers and polymers created by the ribosome, on the ribosome and for the ribosome. Synthesis of increasingly longer products was iteratively coupled with lengthening and maturation of the ribosomal exit tunnel. Protein catalysis appears to be a late byproduct of selection for sophisticated and finely controlled assembly.

Keywords: origin of life; origins of protein folding; protein evolution; ribosomal origins and evolution; ribosomal protein; β-harpin.

Fig. 1

(A) The rRNA of the large subunit of the T. thermophilus ribosome colored by relative age. Phase 1, the most ancient phase, is dark blue. Phase 2 is light blue. Phase 3 is green. Phase 4 is yellow. Phase 5 is orange. Phase 6, the most recent prokaryotic phase, is red. rProteins are grey. (B) The orientation is maintained but rRNA is colored in light grey, universal rProteins are colored by evolutionary phase, and bacterial rProteins are colored dark grey. Phases 3 (green) and 4 (yellow) are shown in cartoon representation. Phases 5 (orange) and 6 (red) are shown in surface representation. From PDB entry 1VY4.

Fig. 2

The history of protein folding illustrated by LSU rProteins uL22 (top) and uL13 (bottom). rProtein segments are colored by their phase, in accordance with rRNA and rProtein phases in figure 1. Segment boundaries are indicated by dashed lines. rProtein uL22 has segments in Phases 4 and 5. uL13 has segments in Phases 3, 4, and 6. The Phase 3 segment of uL13 is random coil. Phase 4 segments of uL22 and uL13 contain isolated β − β structures. The Phase 5 and 6 segments of uL22 and uL13 contain globular domains with extensive intramolecular hydrogen bonds and reduced solvent accessible surface area. These domains contain hydrophobic cores and hydrophilic surfaces. rProtein segments in lower numbered phases are more ancient than those in higher numbered phases. Structures are extracted from the T. thermophilus ribosome.

Fig. 3

Structural attributes of rProtein segments in Phases 3–6 of ribosomal evolution. The number of IMHB^BA per amino acid is plotted in red and the SSA per amino acid is plotted in blue. IMHB^BA increases from Phase 3 through 6, indicating increase in secondary structure. SSA, calculated when rRNA is computationally omitted, decreases from Phase 3 through 6, indicating collapse to globular domains. rProteins are from the T. thermophilus ribosome.

Fig. 4

Protein structural elements (coil, β-sheet and α-helix) decomposed in Phases 3–6 of ribosomal evolution. Protein segments transition from random coil to secondary structure from Phase 3 to Phase 4. Secondary structure converts from predominantly β-strand in Phase 4 and 5 to mixed β-strand and α-helix in Phase 6. The area of each pie chart is proportional to the number of amino acids within that phase. Structures are from the T. thermophilus ribosome.

Fig. 5

A folding fitness peak describing relationships of protein folding, fitness, and ribosomal development. The color of the surface indicates the phase of ribosomal evolution. Fitness is maximized where proteins fold to complex three-dimensional structures. Representative rProtein segments, also colored by phase are shown above the funnel. The rProtein segments shown here were extracted from appropriate phase of the T. thermophilus ribosome.