Missing-link Fold Reveals The Evolutionary Pathway Between RNA Polymerase And Ribosomal Proteins

Numerous molecular machines are required to drive the central dogma of molecular biology. However, the means by which such numerous proteins emerged in the early evolutionary stage of life remains enigmatic.

Many of them possess small β-barrel folds with different topologies, represented by DPBB conserved in DNA and RNA polymerases, and RIFT, OB, and SH3 in ribosomal proteins. Here, we discovered that the previously reconstructed ancient DPBB sequence could also adopt a novel β-barrel fold named DZBB, which shares similarities with RIFT and OB.

Indeed, DZBB could be transformed into them through simple engineering experiments. Furthermore, the OB designs could be converted into SH3 by circular-permutation. These results indicate that these β-barrels diversified quickly from a common ancestor at the beginning of the central dogma evolution.

Experimental reconstruction of the evolutionary pathway between the DZBB, OB, and SH3 folds. (A) Superimposed structures of the single subunit of mk2h_DMILPYS in the DZBB-fold and the OB domain of the ribosomal protein L2 from Thermococcus kodakarensis. (B) Comparison of the topologies of the DZBB and OB folds. In the OB fold, the non-essential secondary elements a1 and b5 are shown as dashed lines. (C) Multiple sequence alignment of the DZBB-OB chimeric proteins with the parent DZBB protein, Ph1. The identical residues with Ph1 are colored purple. The two significantly different segments between tkoL2_v1.2 (OB) and Ph1 (DZBB) are highlighted in gray. (D–G) Crystal structures and topological images of (D) tkoL2_v1, (E) tkoL2_v1.2, (F) tkoL2_v1.2_Z, and (G) mkaL2_v1_SH3. The flows of the engineering procedures are shown as arrows. — Biorxiv.org

Missing-link Fold Reveals The Evolutionary Pathway Between RNA Polymerase And Ribosomal Proteins Biorxiv.org (open access)

Astrobiology