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Title: Defining the mRNA recognition signature of a bacterial toxin protein

Abstract

Bacteria contain multiple type II toxins that selectively degrade mRNAs bound to the ribosome to regulate translation and growth and facilitate survival during the stringent response. Ribosome-dependent toxins recognize a variety of three-nucleotide codons within the aminoacyl (A) site, but how these endonucleases achieve substrate specificity remains poorly understood. In this paper, we identify the critical features for how the host inhibition of growth B (HigB) toxin recognizes each of the three A-site nucleotides for cleavage. X-ray crystal structures of HigB bound to two different codons on the ribosome illustrate how HigB uses a microbial RNase-like nucleotide recognition loop to recognize either cytosine or adenosine at the second A-site position. Strikingly, a single HigB residue and 16S rRNA residue C1054 form an adenosine-specific pocket at the third A-site nucleotide, in contrast to how tRNAs decode mRNA. Finally, our results demonstrate that the most important determinant for mRNA cleavage by ribosome-dependent toxins is interaction with the third A-site nucleotide.

Authors:
 [1];  [1];  [1];  [1];  [1]
  1. Emory Univ., Atlanta, GA (United States). School of Medicine. Dept. of Biochemistry
Publication Date:
Research Org.:
Emory Univ., Atlanta, GA (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Science Foundation (NSF); National Inst. of Health (NIH) (United States)
OSTI Identifier:
1226369
Grant/Contract Number:  
AC02-06CH11357; 0953714; 5T32GM8367; GM108351; RR-15301
Resource Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 112; Journal Issue: 45; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; toxin–antitoxin systems; protein synthesis; RNases; stringent response; ribosome

Citation Formats

Schureck, Marc A., Dunkle, Jack A., Maehigashi, Tatsuya, Miles, Stacey J., and Dunham, Christine M. Defining the mRNA recognition signature of a bacterial toxin protein. United States: N. p., 2015. Web. doi:10.1073/pnas.1512959112.
Schureck, Marc A., Dunkle, Jack A., Maehigashi, Tatsuya, Miles, Stacey J., & Dunham, Christine M. Defining the mRNA recognition signature of a bacterial toxin protein. United States. https://doi.org/10.1073/pnas.1512959112
Schureck, Marc A., Dunkle, Jack A., Maehigashi, Tatsuya, Miles, Stacey J., and Dunham, Christine M. Tue . "Defining the mRNA recognition signature of a bacterial toxin protein". United States. https://doi.org/10.1073/pnas.1512959112. https://www.osti.gov/servlets/purl/1226369.
@article{osti_1226369,
title = {Defining the mRNA recognition signature of a bacterial toxin protein},
author = {Schureck, Marc A. and Dunkle, Jack A. and Maehigashi, Tatsuya and Miles, Stacey J. and Dunham, Christine M.},
abstractNote = {Bacteria contain multiple type II toxins that selectively degrade mRNAs bound to the ribosome to regulate translation and growth and facilitate survival during the stringent response. Ribosome-dependent toxins recognize a variety of three-nucleotide codons within the aminoacyl (A) site, but how these endonucleases achieve substrate specificity remains poorly understood. In this paper, we identify the critical features for how the host inhibition of growth B (HigB) toxin recognizes each of the three A-site nucleotides for cleavage. X-ray crystal structures of HigB bound to two different codons on the ribosome illustrate how HigB uses a microbial RNase-like nucleotide recognition loop to recognize either cytosine or adenosine at the second A-site position. Strikingly, a single HigB residue and 16S rRNA residue C1054 form an adenosine-specific pocket at the third A-site nucleotide, in contrast to how tRNAs decode mRNA. Finally, our results demonstrate that the most important determinant for mRNA cleavage by ribosome-dependent toxins is interaction with the third A-site nucleotide.},
doi = {10.1073/pnas.1512959112},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 45,
volume = 112,
place = {United States},
year = {Tue Oct 27 00:00:00 EDT 2015},
month = {Tue Oct 27 00:00:00 EDT 2015}
}

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