Molecular evolution of protein-RNA mimicry as a mechanism for translational control

Nucleic Acids Research
Assaf KatzMichael Ibba

Abstract

Elongation factor P (EF-P) is a conserved ribosome-binding protein that structurally mimics tRNA to enable the synthesis of peptides containing motifs that otherwise would induce translational stalling, including polyproline. In many bacteria, EF-P function requires post-translational modification with (R)-β-lysine by the lysyl-tRNA synthetase paralog PoxA. To investigate how recognition of EF-P by PoxA evolved from tRNA recognition by aminoacyl-tRNA synthetases, we compared the roles of EF-P/PoxA polar contacts with analogous interactions in a closely related tRNA/synthetase complex. PoxA was found to recognize EF-P solely via identity elements in the acceptor loop, the domain of the protein that interacts with the ribosome peptidyl transferase center and mimics the 3'-acceptor stem of tRNA. Although the EF-P acceptor loop residues required for PoxA recognition are highly conserved, their conservation was found to be independent of the phylogenetic distribution of PoxA. This suggests EF-P first evolved tRNA mimicry to optimize interactions with the ribosome, with PoxA-catalyzed aminoacylation evolving later as a secondary mechanism to further improve ribosome binding and translation control.

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Citations

Sep 30, 2015·Molecular Microbiology·Jürgen LassakKirsten Jung
Apr 16, 2015·Nature Reviews. Microbiology·Kenneth C Keiler
May 14, 2016·Molecular Microbiology·Assaf KatzMichael Ibba
Feb 6, 2020·FEMS Microbiology Reviews·Katherine R Hummels, Daniel B Kearns
Nov 17, 2016·Proceedings of the National Academy of Sciences of the United States of America·Aaron R GallLaszlo N Csonka
Sep 7, 2018·Journal of the Royal Society, Interface·Steven E Massey, Bud Mishra
Sep 10, 2017·Annual Review of Microbiology·Andrei Rajkovic, Michael Ibba
Jan 4, 2020·Journal of Cell Science·Shreya Ahana AyyubZofia M Chrzanowska-Lightowlers
Jun 11, 2019·Frontiers in Microbiology·Wolfram VolkweinJürgen Lassak
May 14, 2021·Nature Communications·Updesh DixitGanjam V Kalpana

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Methods Mentioned

BETA
aminoacylation
PISA
aminoacylate
electrophoresis

Software Mentioned

1asy
WebLogo
Protein Variability Server
PyMOL Molecular Graphics System
GluQRS
EMBOSS
PROMALS3D

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