The Bacterial YbaK Protein Is a Cys-tRNAPro andCys-tRNACysDeacylase

Ruan, Benfang; Söll, Dieter

doi:10.1074/jbc.m502174200

Cited by 83 publications

(96 citation statements)

References 33 publications

(37 reference statements)

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“…Although some of these single-domain homologs have been shown to carry out functions unrelated to tRNA charging (35,36) others, such as YbaK and PrdX, have clearly been shown to possess aminoacylation or editing activity (22,23,25,28,29,31,37). Free-standing editing proteins found in nature appear to have evolved alternate mechanisms to function as efficient and specific editing modules in trans (23,28,29,31). Precisely how they accomplish this in vivo is an open question, but plausible mechanisms include noncovalent interactions with synthetases (38) or other factors.…”

Section: Discussionmentioning

confidence: 99%

“…However, freestanding proteins with homology to the INS domain are found in the genomes of representative species from all three kingdoms of life (25,28 (25,31). In addition to these free-standing ProRS-like editing proteins, a module with homology to the INS domain is appended to the N terminus of yeast and other lower eukaryotic ProRSs (27,28).…”

Section: Discussionmentioning

confidence: 99%

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Restoring species-specific posttransfer editing activity to a synthetase with a defunct editing domain

SternJohn

Hati

Siliciano

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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In contrast, the isolated INS domain displays only weak editing activity and lacks tRNA sequence specificity. These results emphasize the modular nature of synthetase editing active sites and demonstrate how in evolution, a weak editing activity can be converted to a more robust state through fusion to the body of a synthetase. In this manner, a single editing module can be distributed to different synthetases, and simultaneously acquire specificity and enhanced activity.Prolyl-tRNA synthetase ͉ Saccharomyces cerevisiae

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Restoring species-specific posttransfer editing activity to a synthetase with a defunct editing domain

SternJohn

Hati

Siliciano

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition to the INS domain of bacterial ProRS, phylogenetic analysis using available sequences in the Protein Data Bank indicates that members of this superfamily include at least five distinct freestanding protein domains designated YbaK, YeaK, ProX, PrdX, and PA2301. Despite their relatively low sequence identity, these proteins possess high structural homology (16,34,35 (29,32). In contrast, Clostridium sticklandii PrdX has been reported to display Ala-tRNA Pro deacylation specificity (37).…”

Section: Sequence Analysis Of the Ybak Superfamily-freestandingmentioning

confidence: 99%

“…Thus, it is likely that a distinct post-transfer editing mechanism that does not rely on steric exclusion is needed to clear mischarged Cys-tRNA Pro . Indeed, the latter is hydrolyzed by a freestanding domain known as YbaK, which is proposed to function in collaboration with ProRS in trans (29,32,33).…”

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confidence: 99%

Substrate-mediated Fidelity Mechanism Ensures Accurate Decoding of Proline Codons

Kumar

et al. 2011

Journal of Biological Chemistry

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Aminoacyl-tRNA synthetases attach specific amino acids to cognate tRNAs. Prolyl-tRNA synthetases are known to mischarge tRNA Pro with the smaller amino acid alanine and with cysteine, which is the same size as proline. Quality control in proline codon translation is partly ensured by an editing domain (INS) present in most bacterial prolyl-tRNA synthetases that hydrolyzes smaller Ala-tRNA Pro Aminoacyl-tRNA synthetases (aaRSs) 3 play a pivotal role in the decoding of genetic information by catalyzing the esterification of cognate amino acids onto specific transfer RNAs (tRNAs) in a two-step reaction (1). The first step involves amino acid activation with ATP to form an aminoacyl-adenylate intermediate and concomitant pyrophosphate release. The second step involves aminoacyl transfer to the cognate tRNA via a transesterification reaction. Although aaRSs display high substrate specificity, they often misactivate structurally similar amino acids. If left unchecked, these mistakes lead to errors in protein synthesis, and accumulation of such errors can be deleterious to cells (2, 3).To ensure high fidelity in translation, aaRSs have evolved several proofreading mechanisms (4 -7). In the first type of proofreading, misactivated aminoacyl-adenylates are enzymatically hydrolyzed or selectively released from the active site followed by solvent hydrolysis, in a process termed "pretransfer" editing. Another mechanism of proofreading known as "posttransfer" editing is generally believed to function via the socalled "double-sieve" mechanism (8). The model predicted that, whereas one active site could not completely discriminate Ile and Val, two separate active sites with distinct strategies for recognition could significantly enhance fidelity. The aminoacylation active site of the aaRS would act as a "coarse" sieve for adenylate synthesis, activating the cognate amino acid but also allowing, to a lesser extent, activation of isosteric or smaller amino acids that could fit into the amino acid binding pocket. The second "fine" sieve would selectively bind misactivated amino acids for editing while excluding the original cognate amino acid. Thus, substrates synthesized in the first sieve would be further screened by the second sieve to enhance fidelity. Subsequently, biochemical and structural data validated this steric exclusion mechanism for valyl-tRNA synthetase and isoleucyl-tRNA synthetase (9, 10). Indeed, members of both classes of synthetases are now known to possess a second active site spatially separated from the ancient catalytic core to carry out post-transfer editing. Structures of class I isoleucyl-tRNA synthetase (10), leucyl-tRNA synthetase (11), and valyl-tRNA synthetase (12) reveal the highly conserved connective peptide 1 domain that functions in editing. Class II alanyl-tRNA synthetase (AlaRS) (13, 14), threonyl-tRNA synthetase (15), prolyltRNA synthetase (ProRS) (16,17), and phenylalanyl-tRNA synthetase (18, 19) also possess distinct domains for post-transfer editing. A recent study of AlaRS revealed an ...

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“…3), mischarged tRNA is hydrolyzed in an aaRS domain that is distinct from the synthetic aminoacylation domain (9)(10)(11)(12)(13)(14)(15)(16). In addition, editing of mischarged tRNA can occur in trans by independent proteins that function as tRNA-specific deacylases (17,18):…”

mentioning

confidence: 99%

Leucyl-tRNA synthetase editing domain functions as a molecular rheostat to control codon ambiguity in Mycoplasma pathogens

Palencia

Lukk³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Mycoplasma leucyl-tRNA synthetases (LeuRSs) have been identified in which the connective polypeptide 1 (CP1) amino acid editing domain that clears mischarged tRNAs are missing (Mycoplasma mobile) or highly degenerate (Mycoplasma synoviae). Thus, these enzymes rely on a clearance pathway called pretransfer editing, which hydrolyzes misactivated aminoacyl-adenylate intermediate via a nebulous mechanism that has been controversial for decades. Even as the sole fidelity pathway for clearing amino acid selection errors in the pathogenic M. mobile, pretransfer editing is not robust enough to completely block mischarging of tRNA Leu , resulting in codon ambiguity and statistical proteins. A high-resolution X-ray crystal structure shows that M. mobile LeuRS structurally overlaps with other LeuRS cores. However, when CP1 domains from different aminoacyl-tRNA synthetases and origins were fused to this common LeuRS core, surprisingly, pretransfer editing was enhanced. It is hypothesized that the CP1 domain evolved as a molecular rheostat to balance multiple functions. These include distal control of specificity and enzyme activity in the ancient canonical core, as well as providing a separate hydrolytic active site for clearing mischarged tRNA.protein evolution | quality control | statistical proteins | aminoacylation | translation

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The Bacterial YbaK Protein Is a Cys-tRNAPro andCys-tRNACysDeacylase

Cited by 83 publications

References 33 publications

Restoring species-specific posttransfer editing activity to a synthetase with a defunct editing domain

Restoring species-specific posttransfer editing activity to a synthetase with a defunct editing domain

Substrate-mediated Fidelity Mechanism Ensures Accurate Decoding of Proline Codons

Leucyl-tRNA synthetase editing domain functions as a molecular rheostat to control codon ambiguity in Mycoplasma pathogens

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