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tRNA shape is an identity element for an archaeal pyrrolysyl-tRNA synthetase from the human gut

Krahn, Natalie (författare)
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
Zhang, Jingji (författare)
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
Melnikov, Sergey V. (författare)
Biosciences Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
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Tharp, Jeffery M. (författare)
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
Villa, Alessandra (författare)
KTH,Parallelldatorcentrum, PDC
Patel, Armaan (författare)
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
Howard, Rebecca J., 1980- (författare)
Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Solna, SE-171 65, Sweden
Gabir, Haben (författare)
Department of Chemistry, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
Patel, Trushar R. (författare)
Department of Chemistry and Biochemistry, Alberta RNA Research and Training Institute, University of Lethbridge, Lethbridge, AB T1K 2E1, Canada; Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB T6G 2E1, Canada; Department of Microbiology, Immunology & Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
Stetefeld, Jörg (författare)
Department of Chemistry, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; Department of Microbiology, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
Puglisi, Joseph (författare)
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
Söll, Dieter (författare)
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA; Department of Chemistry, Yale University, New Haven, CT 06520, USA
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 (creator_code:org_t)
Oxford University Press (OUP), 2024
2024
Engelska.
Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 52:2, s. 513-524
Relaterad länk:
https://doi.org/10.1...
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https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Protein translation is orchestrated through tRNA aminoacylation and ribosomal elongation. Among the highly conserved structure of tRNAs, they have distinguishing features which promote interaction with their cognate aminoacyl tRNA synthetase (aaRS). These key features are referred to as identity elements. In our study, we investigated the tRNA:aaRS pair that installs the 22nd amino acid, pyrrolysine (tRNAPyl:PylRS). Pyrrolysyl-tRNA synthetases (PylRSs) are naturally encoded in some archaeal and bacterial genomes to acylate tRNAPyl with pyrrolysine. Their large amino acid binding pocket and poor recognition of the tRNA anticodon have been instrumental in incorporating >200 noncanonical amino acids. PylRS enzymes can be divided into three classes based on their genomic structure. Two classes contain both an N-terminal and C-terminal domain, however the third class (ΔpylSn) lacks the N-terminal domain. In this study we explored the tRNA identity elements for a ΔpylSn tRNAPyl from Candidatus Methanomethylophilus alvus which drives the orthogonality seen with its cognate PylRS (MaPylRS). From aminoacylation and translation assays we identified five key elements in ΔpylSn tRNAPyl necessary for MaPylRS activity. The absence of a base (position 8) and a G-U wobble pair (G28:U42) were found to affect the high-resolution structure of the tRNA, while molecular dynamic simulations led us to acknowledge the rigidity imparted from the G-C base pairs (G3:C70 and G5:C68).

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

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