Journal article

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

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

JOURNAL OF BIOLOGICAL CHEMISTRY | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2017

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. Although 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 mammali..

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Grants

Awarded by National Institutes of Health


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Funding Acknowledgements

We thank the staff of beamline MX2 at the Australian Synchrotron for assistance with X-ray data collection. We acknowledge the Consortium for Functional Glycomics funded by National Institutes of Health Grants GM62116 and GM98791 NIGMS for services provided by the Glycan Array Synthesis Core (The Scripps Research Institute, La Jolla, CA) that produced the mammalian glycan microarray and the Protein-Glycan Interaction Core (Emory University School of Medicine, Atlanta, GA) that assisted with analysis of samples on the array. We thank Natasha Ng for initially cloning EcPltAB.