Defining the mRNA recognition signature of a bacterial toxin protein

Schureck, Marc A.; Dunkle, Jack A.; Maehigashi, Tatsuya; Miles, Stacey J.; Dunham, Christine M.

doi:10.1073/pnas.1512959112

Defining the mRNA recognition signature of a bacterial toxin protein

Journal Article · Tue Oct 27 00:00:00 EDT 2015 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1512959112· OSTI ID:1226369

Schureck, Marc A. ^[1]; Dunkle, Jack A. ^[1]; Maehigashi, Tatsuya ^[1]; Miles, Stacey J. ^[1]; Dunham, Christine M. ^[1]

Emory Univ., Atlanta, GA (United States). School of Medicine. Dept. of Biochemistry

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.

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Research Organization:: Emory Univ., Atlanta, GA (United States)

Sponsoring Organization:: National Inst. of Health (NIH) (United States); National Science Foundation (NSF) (United States); USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1226369

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 45 Vol. 112; ISSN 0027-8424

Publisher:: National Academy of Sciences, Washington, DC (United States)Copyright Statement

Country of Publication:: United States

Language:: ENGLISH

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59 BASIC BIOLOGICAL SCIENCES
RNases
protein synthesis
ribosome
stringent response
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Defining the mRNA recognition signature of a bacterial toxin protein

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