Structure based hypothesis of a mitochondrial ribosome rescue mechanism.

Biology Direct
Martijn HuynenSander B Nabuurs

Abstract

mtRF1 is a vertebrate mitochondrial protein with an unknown function that arose from a duplication of the mitochondrial release factor mtRF1a. To elucidate the function of mtRF1, we determined the positions that are conserved among mtRF1 sequences but that are different in their mtRF1a paralogs. We subsequently modeled the 3D structure of mtRF1a and mtRF1 bound to the ribosome, highlighting the structural implications of these differences to derive a hypothesis for the function of mtRF1. Our model predicts, in agreement with the experimental data, that the 3D structure of mtRF1a allows it to recognize the stop codons UAA and UAG in the A-site of the ribosome. In contrast, we show that mtRF1 likely can only bind the ribosome when the A-site is devoid of mRNA. Furthermore, while mtRF1a will adopt its catalytic conformation, in which it functions as a peptidyl-tRNA hydrolase in the ribosome, only upon binding of a stop codon in the A-site, mtRF1 appears specifically adapted to assume this extended, peptidyl-tRNA hydrolyzing conformation in the absence of mRNA in the A-site. We predict that mtRF1 specifically recognizes ribosomes with an empty A-site and is able to function as a peptidyl-tRNA hydrolase in those situations. Stalled ...Continue Reading

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Citations

Jun 13, 2012·Molecular Biology and Evolution·Isabel DuarteMartijn Huynen
Nov 17, 2015·Life·Ana R BezerraManuel A S Santos
Aug 21, 2012·Biochimica Et Biophysica Acta·Martijn A HuynenRadek Szklarczyk
Aug 8, 2014·Frontiers in Microbiology·Maria T WesolowskaZofia M A Chrzanowska-Lightowlers
Jan 21, 2016·Annual Review of Biochemistry·Martin OttAlan Brown
Jun 19, 2015·PLoS Genetics·Zofia Maria Chrzanowska-Lightowlers, Robert Neil Lightowlers
May 23, 2015·Journal of Neurology, Neurosurgery, and Psychiatry·Eri ImagawaNaomichi Matsumoto
Jun 2, 2020·Genetics and Molecular Biology·Eduardo PerroneCecília Micheletti
Mar 9, 2018·Nucleic Acids Research·Marina ToompuuHoward T Jacobs
Jul 22, 2018·Essays in Biochemistry·Aaron R D'Souza, Michal Minczuk
Jan 4, 2020·Journal of Cell Science·Shreya Ahana AyyubZofia M Chrzanowska-Lightowlers

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Software Mentioned

ProtTest
PhyML
ClustalW
Sequence Harmony
YASARA
BLAST
YASARA2
SCWRL

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