Selectivity of stop codon recognition in translation termination is modulated by multiple conformations of GTS loop in eRF1

Translation termination in eukaryotes is catalyzed by two release factors eRF1 and eRF3 in a cooperative manner. The precise mechanism of stop codon discrimination by eRF1 remains obscure, hindering drug development targeting aberrations at translation termination. By solving the solution structures...

Full description

Saved in:
Bibliographic Details
Main Authors: Li, Yan, Pillay, Shubhadra, Frolova, Ludmila, Pervushin, Konstantin, Wong, Leo E.
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2014
Subjects:
Online Access:https://hdl.handle.net/10356/101527
http://hdl.handle.net/10220/18690
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-101527
record_format dspace
spelling sg-ntu-dr.10356-1015272023-02-28T17:04:59Z Selectivity of stop codon recognition in translation termination is modulated by multiple conformations of GTS loop in eRF1 Li, Yan Pillay, Shubhadra Frolova, Ludmila Pervushin, Konstantin Wong, Leo E. School of Biological Sciences DRNTU::Science::Biological sciences Translation termination in eukaryotes is catalyzed by two release factors eRF1 and eRF3 in a cooperative manner. The precise mechanism of stop codon discrimination by eRF1 remains obscure, hindering drug development targeting aberrations at translation termination. By solving the solution structures of the wild-type N-domain of human eRF1 exhibited omnipotent specificity, i.e. recognition of all three stop codons, and its unipotent mutant with UGA-only specificity, we found the conserved GTS loop adopting alternate conformations. We propose that structural variability in the GTS loop may underline the switching between omnipotency and unipotency of eRF1, implying the direct access of the GTS loop to the stop codon. To explore such feasibility, we positioned N-domain in a pre-termination ribosomal complex using the binding interface between N-domain and model RNA oligonucleotides mimicking Helix 44 of 18S rRNA. NMR analysis revealed that those duplex RNA containing 2-nt internal loops interact specifically with helix α1 of N-domain, and displace C-domain from a non-covalent complex of N-domain and C-domain, suggesting domain rearrangement in eRF1 that accompanies N-domain accommodation into the ribosomal A site. MOE (Min. of Education, S’pore) Published version 2014-01-22T06:14:42Z 2019-12-06T20:39:57Z 2014-01-22T06:14:42Z 2019-12-06T20:39:57Z 2012 2012 Journal Article Wong, L. E., Li, Y., Pillay, S., Frolova, L., & Pervushin, K. (2012). Selectivity of stop codon recognition in translation termination is modulated by multiple conformations of GTS loop in eRF1. Nucleic acids research, 40(12), 5751-5765. https://hdl.handle.net/10356/101527 http://hdl.handle.net/10220/18690 10.1093/nar/gks192 22383581 en Nucleic acids research © 2012 The Authors. This paper was published in Nucleic Acids Research and is made available as an electronic reprint (preprint) with permission of the authors. The paper can be found at the following official DOI: [http://dx.doi.org/10.1093/nar/gks192]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Li, Yan
Pillay, Shubhadra
Frolova, Ludmila
Pervushin, Konstantin
Wong, Leo E.
Selectivity of stop codon recognition in translation termination is modulated by multiple conformations of GTS loop in eRF1
description Translation termination in eukaryotes is catalyzed by two release factors eRF1 and eRF3 in a cooperative manner. The precise mechanism of stop codon discrimination by eRF1 remains obscure, hindering drug development targeting aberrations at translation termination. By solving the solution structures of the wild-type N-domain of human eRF1 exhibited omnipotent specificity, i.e. recognition of all three stop codons, and its unipotent mutant with UGA-only specificity, we found the conserved GTS loop adopting alternate conformations. We propose that structural variability in the GTS loop may underline the switching between omnipotency and unipotency of eRF1, implying the direct access of the GTS loop to the stop codon. To explore such feasibility, we positioned N-domain in a pre-termination ribosomal complex using the binding interface between N-domain and model RNA oligonucleotides mimicking Helix 44 of 18S rRNA. NMR analysis revealed that those duplex RNA containing 2-nt internal loops interact specifically with helix α1 of N-domain, and displace C-domain from a non-covalent complex of N-domain and C-domain, suggesting domain rearrangement in eRF1 that accompanies N-domain accommodation into the ribosomal A site.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Li, Yan
Pillay, Shubhadra
Frolova, Ludmila
Pervushin, Konstantin
Wong, Leo E.
format Article
author Li, Yan
Pillay, Shubhadra
Frolova, Ludmila
Pervushin, Konstantin
Wong, Leo E.
author_sort Li, Yan
title Selectivity of stop codon recognition in translation termination is modulated by multiple conformations of GTS loop in eRF1
title_short Selectivity of stop codon recognition in translation termination is modulated by multiple conformations of GTS loop in eRF1
title_full Selectivity of stop codon recognition in translation termination is modulated by multiple conformations of GTS loop in eRF1
title_fullStr Selectivity of stop codon recognition in translation termination is modulated by multiple conformations of GTS loop in eRF1
title_full_unstemmed Selectivity of stop codon recognition in translation termination is modulated by multiple conformations of GTS loop in eRF1
title_sort selectivity of stop codon recognition in translation termination is modulated by multiple conformations of gts loop in erf1
publishDate 2014
url https://hdl.handle.net/10356/101527
http://hdl.handle.net/10220/18690
_version_ 1759858100312997888