PXD011051

PXD011051 is an original dataset announced via ProteomeXchange.

Title	On the mechanism and origin of isoleucyl-tRNA synthetase editing against norvaline
Description	Aminoacyl-tRNA synthetases (aaRSs), the enzymes responsible for coupling tRNAs to their cognate amino acids, minimize translational errors by intrinsic hydrolytic editing. Here, we compared the propensity of norvaline (Nva), a linear amino acid not coded for protein synthesis, to the proteinogenic, branched valine (Val) to mistranslate isoleucine (Ile) in proteins. We show that in the synthetic site of isoleucyl-tRNA synthetase (IleRS), aminoacylation and pre-transfer editing with Nva and Val occur at similar rates. Post-transfer editing was, however, more efficient with Nva as IleRS misaminoacylates Nva-tRNAIle at slower rate than Val-tRNAIle. Accordingly, an Escherichia coli strain lacking IleRS post-transfer editing misincorporated Nva and Val in the proteome to a similar extent and at the same Ile positions. However, Nva mistranslation inflicted higher toxicity than Val, in agreement with IleRS post-transfer editing domain being optimized for hydrolysis of Nva-tRNAIle. Furthermore, we found that the evolutionary related IleRS, leucyl- and valyl-tRNA synthetases (I/L/VRSs), all efficiently hydrolyze Nva-tRNAs even when editing of Nva seems redundant. Thus, we hypothesize that editing of Nva-tRNAs had already existed in the last common ancestor of I/L/VRSs, and that the editing domain of I/L/VRSs had primarily evolved to prevent infiltration of Nva into modern proteins.
HostingRepository	PRIDE
AnnounceDate	2019-01-28
AnnouncementXML	Submission_2019-02-15_04:12:30.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nicolas Nalpas
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	modified L-leucine residue; modified L-isoleucine residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2018-09-10 08:38:11	ID requested
1	2019-01-28 02:24:18	announced
⏵ 2	2019-02-15 04:12:31	announced	Updated publication reference for PubMed record(s): 30711543.

Bilus M, Semanjski M, Mocibob M, Zivkovic I, Cvetesic N, Tawfik DS, Toth-Petroczy A, Macek B, Gruic-Sovulj I, On the Mechanism and Origin of Isoleucyl-tRNA Synthetase Editing against Norvaline. J Mol Biol, 431(6):1284-1297(2019) [pubmed]

submitter keyword: mistranslation, isoleucyl-tRNA synthetase, E. coli

Boris Macek
contact affiliation	Quantitative Proteomics & Proteome Center Tuebingen Interfaculty Institute for Cell Biology University of Tuebingen Tuebingen Germany
contact email	boris.macek@uni-tuebingen.de
lab head
Nicolas Nalpas
contact affiliation	Tuebingen University
contact email	nalpas.nicolas@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011051
     1. Label: PRIDE project
     2. Name: On the mechanism and origin of isoleucyl-tRNA synthetase editing against norvaline