Backbone Brackets and Arginine Tweezers delineate Class I and Class II aminoacyl tRNA synthetases

Abstract

The origin of the machinery that realizes protein biosynthesis in all organisms is still unclear. One key component of this machinery are aminoacyl tRNA synthetases (aaRS), which ligate tRNAs to amino acids while consuming ATP. Sequence analyses revealed that these enzymes can be divided into two complementary classes. Both classes differ significantly on a sequence and structural level, feature different reaction mechanisms, and occur in diverse oligomerization states. The one unifying aspect of both classes is their function of binding ATP. We identified Backbone Brackets and Arginine Tweezers as most compact ATP binding motifs characteristic for each Class. Geometric analysis shows a structural rearrangement of the Backbone Brackets upon ATP binding, indicating a general mechanism of all Class I structures. Regarding the origin of aaRS, the Rodin-Ohno hypothesis states that the peculiar nature of the two aaRS classes is the result of their primordial forms, called Protozymes, being encoded on opposite strands of the same gene. Backbone Brackets and Arginine Tweezers were traced back to the proposed Protozymes and their more efficient successors, the Urzymes. Both structural motifs can be observed as pairs of residues in contemporary structures and it seems that the time of their addition, indicated by their placement in the ancient aaRS, coincides with the evolutionary trace of Proto- and Urzymes.

Hierarchical groove discrimination by Class I and II aminoacyl-tRNA synthetases reveals a palimpsest of the operational RNA code in the tRNA acceptor-stem bases

“…Class II active sites use a pair of conserved arginine side chains to ‘clamp’ the adenosine of ATP in place ( 40 ). The two arginine residues appear also to interact with the 3′-terminal adenosine (Figure 8 ).…”

Characterizing the relation of functional and Early Folding Residues in protein structures using the example of aminoacyl-tRNA synthetases

“…folding initiation sites) were predicted (depicted in blue). EFR are a distinct set of residues with respect to ATP binding sites (orange) identified in a previous study [ 48 ]. Backbone Brackets and Arginine Tweezers are class-specific ATP binding motifs identified in the same study.…”

“…Aminoacyl-tRNA synthetases (aaRS) may be the proteins with the most intriguing evolutionary history and are a prime candidate to analyze as their emergence is well-discussed in literature [ 43 – 48 ]. aaRS enzymes attach amino acids to their cognate tRNA, which is subsequently recognized by its anti-codon and consumed by a ribosome.…”

“…Some organisms may feature additional aaRS such as PylRS which makes pyrrolysine accessible to protein biosynthesis. In a recent study [ 48 ], two ligand binding motifs—the Backbone Brackets and the Arginine Tweezers—were identified as characteristic for each aaRS class. These motifs were furthermore linked to primordial implementations of both aaRS classes called protozymes [ 46 , 47 ].…”

“…The Rodin-Ohno hypothesis [ 43 ] proposes that aaRS enzymes were once complementarily encoded by the same gene. This provides an elegant explanation for the emergence and peculiarities of contemporary aaRS classes [ 43 , 46 – 48 ]. It is hypothesized that all aaRS genes originate from this primordial gene encompassing both protozymes.…”