Unique protein architecture of alanyl-tRNA synthetase for aminoacylation, editing, and dimerization

Naganuma, Masahiro; Sekine, S.; Fukunaga, Ryuya; Yokoyama, Shigeyuki

doi:10.1073/pnas.0901572106

Cited by 52 publications

(70 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This base pair is the recognition site for alanyl-tRNA synthetase. 25 Juxtaposed to P1 is a 3-10 bp long helix corresponding to the tRNA anticodon stem, referred here to as P2 (Fig. 4A).…”

Section: Resultsmentioning

confidence: 99%

A second eukaryotic group with mitochondrion-encoded tmRNA

et al. 2013

View full text Add to dashboard Cite

“…This base pair is the recognition site for alanyl-tRNA synthetase. 25 Juxtaposed to P1 is a 3-10 bp long helix corresponding to the tRNA anticodon stem, referred here to as P2 (Fig. 4A).…”

Section: Resultsmentioning

confidence: 99%

A second eukaryotic group with mitochondrion-encoded tmRNA

et al. 2013

View full text Add to dashboard Cite

“…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 exception to the size exclusion-based double-sieve model of editing.…”

mentioning

confidence: 99%

Substrate-mediated Fidelity Mechanism Ensures Accurate Decoding of Proline Codons

Kumar

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

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 ...

show abstract

“…The model is composed of three -helices and a large -sheet, in which the first and second -strands are arranged in parallel; and the third and fourth are anti-parallel. Interestingly, the model is somewhat similar to that of the aminoacyl-tRNA synthetase editing domain (Ribas de Pouplana & Schimmel, 2000;Naganuma et al, 2009). The phylogenetic relationships amongst these enzymes are clustered around substrate specificity (Guo et al, 2009).…”

Section: Novel Sources?mentioning

confidence: 81%