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What RNA World? Why a Peptide/RNA Partnership Merits Renewed Experimental Attention.

Carter CW - Life (Basel) (2015)

Bottom Line: We review arguments that biology emerged from a reciprocal partnership in which small ancestral oligopeptides and oligonucleotides initially both contributed rudimentary information coding and catalytic rate accelerations, and that the superior information-bearing qualities of RNA and the superior catalytic potential of proteins emerged from such complexes only with the gradual invention of the genetic code.Parallel hierarchical catalytic repertoires for increasingly highly conserved sequences from the two synthetase classes now increase the likelihood that they arose as translation products from opposite strands of a single gene.Sense/antisense coding affords a new bioinformatic metric for phylogenetic relationships much more distant than can be reconstructed from multiple sequence alignments of a single superfamily.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7260, USA. carter@med.unc.edu.

ABSTRACT
We review arguments that biology emerged from a reciprocal partnership in which small ancestral oligopeptides and oligonucleotides initially both contributed rudimentary information coding and catalytic rate accelerations, and that the superior information-bearing qualities of RNA and the superior catalytic potential of proteins emerged from such complexes only with the gradual invention of the genetic code. A coherent structural basis for that scenario was articulated nearly a decade before the demonstration of catalytic RNA. Parallel hierarchical catalytic repertoires for increasingly highly conserved sequences from the two synthetase classes now increase the likelihood that they arose as translation products from opposite strands of a single gene. Sense/antisense coding affords a new bioinformatic metric for phylogenetic relationships much more distant than can be reconstructed from multiple sequence alignments of a single superfamily. Evidence for distinct coding properties in tRNA acceptor stems and anticodons, and experimental demonstration that the two synthetase family ATP binding sites can indeed be coded by opposite strands of the same gene supplement these biochemical and bioinformatic data, establishing a solid basis for key intermediates on a path from simple, stereochemically coded, reciprocally catalytic peptide/RNA complexes through the earliest peptide catalysts to contemporary aminoacyl-tRNA synthetases. That scenario documents a path to increasing complexity that obviates the need for a single polymer to act both catalytically and as an informational molecule.

No MeSH data available.


Related in: MedlinePlus

Urzymes isolated from Class I TrpRS (130 amino acids) and Class II HisRS (124 amino acids). (a) Monomer architectures. Both enzymes are dimeric. Monomers consist of two consensus domains, catalytic and anticodon-binding (ABD). The 46-amino acid ATP binding sites are blue and bounded by transparent surfaces; the remainder of the Urzymes are red. Catalytic domains of both also include insertions, colored amber. Active-site ligands are shown as spheres; (b) Secondary structures are dissimilar; Class I is a Rossmann fold with parallel β-strands; Class II is an antiparallel structure; (c) Amino acid (yellow) and ATP (cyan) substrates are spheres. Stick models of Class I-defining signatures PxxxxHIGH (green) and KMSKS (red) and Class II Motif 2 (green) are surrounded by transparent surfaces to reveal catalytically important interactions with ATP. The cartoons are based on crystal structures of the full-length enzymes. However, long-time MD simulations of both Urzymes in the presence of both substrates have shown that the structures shown here persist, but that in the absence of tryptophan the Class I specificity helix above the bound tryptophan re-orients, removing several key interactions involved in specific recognition [21,25,26].
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life-05-00294-f003: Urzymes isolated from Class I TrpRS (130 amino acids) and Class II HisRS (124 amino acids). (a) Monomer architectures. Both enzymes are dimeric. Monomers consist of two consensus domains, catalytic and anticodon-binding (ABD). The 46-amino acid ATP binding sites are blue and bounded by transparent surfaces; the remainder of the Urzymes are red. Catalytic domains of both also include insertions, colored amber. Active-site ligands are shown as spheres; (b) Secondary structures are dissimilar; Class I is a Rossmann fold with parallel β-strands; Class II is an antiparallel structure; (c) Amino acid (yellow) and ATP (cyan) substrates are spheres. Stick models of Class I-defining signatures PxxxxHIGH (green) and KMSKS (red) and Class II Motif 2 (green) are surrounded by transparent surfaces to reveal catalytically important interactions with ATP. The cartoons are based on crystal structures of the full-length enzymes. However, long-time MD simulations of both Urzymes in the presence of both substrates have shown that the structures shown here persist, but that in the absence of tryptophan the Class I specificity helix above the bound tryptophan re-orients, removing several key interactions involved in specific recognition [21,25,26].

Mentions: “Urzymes” are quite small, highly conserved fragments of the two aminoacyl-tRNA synthetase superfamilies (Figure 3). Our biochemical studies have shown that Urzymes from both classes retain ~60% of the Gibbs energies of catalytic proficiency of fully evolved synthetases [13,14,21] and ~20% of their specificities for amino acid activation [12,20]. The catalytic power of peptides related by phylogeny to contemporary enzymes is thus far greater than was anticipated from comparison with the uncatalyzed rate of peptide bond formation, which is ~106-fold slower [22,23]. This million-fold excess catalytic proficiency argues (i) that such constructs closely resemble true ancestral forms; (ii) that they are themselves highly evolved; and (iii) hence had simpler functional ancestors that might now themselves be experimentally accessible. Second, and less obvious, we showed that synthetase Urzyme coding sequences have a property—high middle-codon base-pairing—expected if these two distinct enzyme families were once encoded on opposite strands of the same ancestral gene [17], as proposed by Rodin and Ohno [8,24]. This new metric can therefore also be used to pursue the histories of ancient genes further back into the depths of time than ever before.


What RNA World? Why a Peptide/RNA Partnership Merits Renewed Experimental Attention.

Carter CW - Life (Basel) (2015)

Urzymes isolated from Class I TrpRS (130 amino acids) and Class II HisRS (124 amino acids). (a) Monomer architectures. Both enzymes are dimeric. Monomers consist of two consensus domains, catalytic and anticodon-binding (ABD). The 46-amino acid ATP binding sites are blue and bounded by transparent surfaces; the remainder of the Urzymes are red. Catalytic domains of both also include insertions, colored amber. Active-site ligands are shown as spheres; (b) Secondary structures are dissimilar; Class I is a Rossmann fold with parallel β-strands; Class II is an antiparallel structure; (c) Amino acid (yellow) and ATP (cyan) substrates are spheres. Stick models of Class I-defining signatures PxxxxHIGH (green) and KMSKS (red) and Class II Motif 2 (green) are surrounded by transparent surfaces to reveal catalytically important interactions with ATP. The cartoons are based on crystal structures of the full-length enzymes. However, long-time MD simulations of both Urzymes in the presence of both substrates have shown that the structures shown here persist, but that in the absence of tryptophan the Class I specificity helix above the bound tryptophan re-orients, removing several key interactions involved in specific recognition [21,25,26].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390853&req=5

life-05-00294-f003: Urzymes isolated from Class I TrpRS (130 amino acids) and Class II HisRS (124 amino acids). (a) Monomer architectures. Both enzymes are dimeric. Monomers consist of two consensus domains, catalytic and anticodon-binding (ABD). The 46-amino acid ATP binding sites are blue and bounded by transparent surfaces; the remainder of the Urzymes are red. Catalytic domains of both also include insertions, colored amber. Active-site ligands are shown as spheres; (b) Secondary structures are dissimilar; Class I is a Rossmann fold with parallel β-strands; Class II is an antiparallel structure; (c) Amino acid (yellow) and ATP (cyan) substrates are spheres. Stick models of Class I-defining signatures PxxxxHIGH (green) and KMSKS (red) and Class II Motif 2 (green) are surrounded by transparent surfaces to reveal catalytically important interactions with ATP. The cartoons are based on crystal structures of the full-length enzymes. However, long-time MD simulations of both Urzymes in the presence of both substrates have shown that the structures shown here persist, but that in the absence of tryptophan the Class I specificity helix above the bound tryptophan re-orients, removing several key interactions involved in specific recognition [21,25,26].
Mentions: “Urzymes” are quite small, highly conserved fragments of the two aminoacyl-tRNA synthetase superfamilies (Figure 3). Our biochemical studies have shown that Urzymes from both classes retain ~60% of the Gibbs energies of catalytic proficiency of fully evolved synthetases [13,14,21] and ~20% of their specificities for amino acid activation [12,20]. The catalytic power of peptides related by phylogeny to contemporary enzymes is thus far greater than was anticipated from comparison with the uncatalyzed rate of peptide bond formation, which is ~106-fold slower [22,23]. This million-fold excess catalytic proficiency argues (i) that such constructs closely resemble true ancestral forms; (ii) that they are themselves highly evolved; and (iii) hence had simpler functional ancestors that might now themselves be experimentally accessible. Second, and less obvious, we showed that synthetase Urzyme coding sequences have a property—high middle-codon base-pairing—expected if these two distinct enzyme families were once encoded on opposite strands of the same ancestral gene [17], as proposed by Rodin and Ohno [8,24]. This new metric can therefore also be used to pursue the histories of ancient genes further back into the depths of time than ever before.

Bottom Line: We review arguments that biology emerged from a reciprocal partnership in which small ancestral oligopeptides and oligonucleotides initially both contributed rudimentary information coding and catalytic rate accelerations, and that the superior information-bearing qualities of RNA and the superior catalytic potential of proteins emerged from such complexes only with the gradual invention of the genetic code.Parallel hierarchical catalytic repertoires for increasingly highly conserved sequences from the two synthetase classes now increase the likelihood that they arose as translation products from opposite strands of a single gene.Sense/antisense coding affords a new bioinformatic metric for phylogenetic relationships much more distant than can be reconstructed from multiple sequence alignments of a single superfamily.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7260, USA. carter@med.unc.edu.

ABSTRACT
We review arguments that biology emerged from a reciprocal partnership in which small ancestral oligopeptides and oligonucleotides initially both contributed rudimentary information coding and catalytic rate accelerations, and that the superior information-bearing qualities of RNA and the superior catalytic potential of proteins emerged from such complexes only with the gradual invention of the genetic code. A coherent structural basis for that scenario was articulated nearly a decade before the demonstration of catalytic RNA. Parallel hierarchical catalytic repertoires for increasingly highly conserved sequences from the two synthetase classes now increase the likelihood that they arose as translation products from opposite strands of a single gene. Sense/antisense coding affords a new bioinformatic metric for phylogenetic relationships much more distant than can be reconstructed from multiple sequence alignments of a single superfamily. Evidence for distinct coding properties in tRNA acceptor stems and anticodons, and experimental demonstration that the two synthetase family ATP binding sites can indeed be coded by opposite strands of the same gene supplement these biochemical and bioinformatic data, establishing a solid basis for key intermediates on a path from simple, stereochemically coded, reciprocally catalytic peptide/RNA complexes through the earliest peptide catalysts to contemporary aminoacyl-tRNA synthetases. That scenario documents a path to increasing complexity that obviates the need for a single polymer to act both catalytically and as an informational molecule.

No MeSH data available.


Related in: MedlinePlus