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Structure–function analyses of a pertussis-like toxin from pathogenic Escherichia coli reveal a distinct mechanism of inhibition of trimeric G-proteins

Overview of attention for article published in Journal of Biological Chemistry, June 2017
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (95th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

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9 news outlets
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1 X user

Citations

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24 Dimensions

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34 Mendeley
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Title
Structure–function analyses of a pertussis-like toxin from pathogenic Escherichia coli reveal a distinct mechanism of inhibition of trimeric G-proteins
Published in
Journal of Biological Chemistry, June 2017
DOI 10.1074/jbc.m117.796094
Pubmed ID
Authors

Dene R Littler, Sheng Y Ang, Danilo G Moriel, Martina Kocan, Oded Kleifeld, Matthew D Johnson, Mai T Tran, Adrienne W Paton, James C Paton, Roger J Summers, Mark A Schembri, Jamie Rossjohn, Travis Beddoe

Abstract

Pertussis-like toxins are secreted by several bacterial pathogens during infection. They belong to the AB5 virulence factors, which bind to glycans on host cell membranes for internalization. Host cell recognition and internalization are mediated by toxin B subunits sharing a unique pentameric ring-like assembly. While the role of pertussis toxin in whooping cough is well established, pertussis-like toxins produced by other bacteria are less studied and their mechanisms of action are unclear. Here, we report that some extra-intestinal Escherichia coli pathogens (i.e. those that reside in the gut but can spread to other bodily locations) encode a pertussis-like toxin that inhibits mammalian cell growth in vitro. We found that this protein, EcPlt is related to toxins produced by both nontyphoidal and typhoidal Salmonella serovars. Pertussis-like toxins are secreted as disulfide-bonded heterohexamers in which the catalytic ADP-ribosyltransfersase subunit is activated when exposed to the reducing environment in mammalian cells. We found here that the reduced EcPlt exhibits large structural rearrangements associated with its activation. We noted that inhibitory residues tethered within the NAD+-binding site by an intramolecular disulfide in the oxidized state dissociate upon the reduction and enable loop restructuring to form the nucleotide-binding site. Surprisingly, while pertussis toxin targets a cysteine residue within the α-subunit of inhibitory trimeric G proteins, we observed that activated EcPlt toxin modifies a proximal lysine/asparagine residue instead. In conclusion, our results reveal the molecular mechanism underpinning activation of pertussis-like toxins, and we also identified differences in host target specificity.

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The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 34 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 7 21%
Researcher 4 12%
Student > Master 3 9%
Student > Ph. D. Student 2 6%
Student > Doctoral Student 2 6%
Other 2 6%
Unknown 14 41%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 35%
Immunology and Microbiology 3 9%
Chemistry 2 6%
Agricultural and Biological Sciences 1 3%
Arts and Humanities 1 3%
Other 0 0%
Unknown 15 44%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 61. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 February 2018.
All research outputs
#700,384
of 25,382,440 outputs
Outputs from Journal of Biological Chemistry
#316
of 85,247 outputs
Outputs of similar age
#14,729
of 328,273 outputs
Outputs of similar age from Journal of Biological Chemistry
#10
of 375 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 85,247 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one has done particularly well, scoring higher than 99% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 328,273 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 95% of its contemporaries.
We're also able to compare this research output to 375 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.