Seven amino acid types suffice to reconstruct the core fold of RNA polymerase
2023
Yagi, Sota | Padhi, Aditya | Vucinic, Jelena | Barbe, Sophie | Schiex, Thomas | Nakagawa, Reiko | Simoncini, David | Zhang, Kam | Tagami, Shunsuke | RIKEN Center for Biosystems Dynamics Research [Kobe] (RIKEN BDR) ; RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN) | Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRAE) ; Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Toulouse Biotechnology Institute (TBI) ; Institut National des Sciences Appliquées - Toulouse (INSA Toulouse) ; Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Institut de recherche en informatique de Toulouse (IRIT) ; Université Toulouse Capitole (UT Capitole) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J) ; Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI) ; Université Toulouse - Jean Jaurès (UT2J) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)
Abstract The extant complex proteins must have evolved from ancient short and simple ancestors. Nevertheless, how such prototype proteins emerged on the primitive earth remains enigmatic. The double-psi beta-barrel (DPBB) is one of the oldest protein folds and conserved in various fundamental enzymes, such as the core domain of RNA polymerase. Here, by reverse engineering a modern DPBB domain, we reconstructed its evolutionary pathway started by “interlacing homo- dimerization” of a half-size peptide, followed by gene duplication and fusion. Furthermore, by simplifying the amino acid repertoire of the peptide, we successfully created the DPBB fold with only seven amino acid types (Ala, Asp, Glu, Gly, Lys, Arg, and Val), which can be coded by only GNN and ARR (R = A or G) codons in the modern translation system. Thus, the DPBB fold could have been materialized by the early translation system and genetic code.
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