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

Krahn, Natalie; Zhang, Jingji; Melnikov, Sergey V.; Tharp, Jeffery M.; Villa, Alessandra; Patel, Armaan; Howard, Rebecca J; Gabir, Haben; Patel, Trushar R; Stetefeld, Jörg; Puglisi, Joseph; Söll, Dieter

doi:10.1093/nar/gkad1188

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

Journal Article · Thu Dec 14 23:00:00 EST 2023 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkad1188· OSTI ID:2472428

^[1]; Zhang, Jingji ^[2]; Melnikov, Sergey V. ^[3]; Tharp, Jeffery M. ^[4]; Villa, Alessandra ^[5]; Patel, Armaan ^[4]; Howard, Rebecca J ^[6]; Gabir, Haben ^[7]; ^[8]; Stetefeld, Jörg ^[7]; ^[2]; ^[4]

Yale Univ., New Haven, CT (United States); OSTI
Stanford Univ., CA (United States). School of Medicine
Newcastle University, Newcastle upon Tyne (United Kingdom)
Yale Univ., New Haven, CT (United States)
KTH Royal Inst. of Technology, Stockholm (Sweden)
Stockholm Univ. (Sweden)
Univ. of Manitoba, Winnipeg, MB (Canada)
Univ. of Lethbridge, AB (Canada); Univ. of Alberta, Edmonton, AB (Canada); Univ. of Calgary, AB (Canada)

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).

View Accepted Manuscript (DOE)

Research Organization:: Yale Univ., New Haven, CT (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); Cystic Fibrosis Foundation; Canadian Institutes of Health

Grant/Contract Number:: FG02-98ER20311

OSTI ID:: 2472428

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 2 Vol. 52; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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