Conformational change of the Bordetella response regulator BvgA accompanies its activation of the B. pertussis virulence gene fhaB

David Kim; John Tracey; Manuel Becerra Flores; Kanita Chaudhry; Rafae Nasim; Abraham Correa-Medina; Leslie Knipling; Qing Chen; Scott Stibitz; Lisa M.M. Jenkins; Kyung Moon; Tim Cardozo; Deborah M. Hinton

Computational and Structural Biotechnology Journal (Jan 2022)

Conformational change of the Bordetella response regulator BvgA accompanies its activation of the B. pertussis virulence gene fhaB

David Kim,
John Tracey,
Manuel Becerra Flores,
Kanita Chaudhry,
Rafae Nasim,
Abraham Correa-Medina,
Leslie Knipling,
Qing Chen,
Scott Stibitz,
Lisa M.M. Jenkins,
Kyung Moon,
Tim Cardozo,
Deborah M. Hinton

Affiliations

David Kim: Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
John Tracey: Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Manuel Becerra Flores: Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York University Grossman School of Medicine, 455 First Avenue, New York, NY 10016, USA
Kanita Chaudhry: Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Rafae Nasim: Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Abraham Correa-Medina: Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Leslie Knipling: Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Qing Chen: Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA
Scott Stibitz: Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA
Lisa M.M. Jenkins: Collaborative Protein Technology Resource, Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Kyung Moon: Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Tim Cardozo: Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York University Grossman School of Medicine, 455 First Avenue, New York, NY 10016, USA; Corresponding authors.
Deborah M. Hinton: Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding authors.

Journal volume & issue: Vol. 20
pp. 6431 – 6442

Abstract

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The BvgAS two-component system regulates virulence gene expression in Bordetella pertussis. Although precise three-dimensional structural information is not available for the response regulator BvgA, its sequence conservation with E. coli NarL and previous studies have indicated that it is composed of 3 domains: an N-terminal domain (NTD) containing the phosphorylation site, a linker, and a DNA-binding C-terminal domain (CTD). Previous work has determined how BvgACTD dimers interact with the promoter (PfhaB) of fhaB, the gene encoding the virulence adhesin filamentous hemagglutinin. Here we use molecular modeling, FeBABE footprinting, and crosslinking to show that within the transcription complex of phosphorylated BvgA (BvgA ∼ P), B. pertussis RNAP, and PfhaB, the NTDs displace from the CTDs and are positioned at specific locations relative to the three BvgA ∼ P binding sites. Our work identifies a patch of the NTD that faces the DNA and suggests that BvgA ∼ P undergoes a conformational rearrangement that relocates the NTD to allow productive interaction of the CTD with the DNA.

Published in Computational and Structural Biotechnology Journal

ISSN: 2001-0370 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Technology: Chemical technology: Biotechnology
Website: https://www.journals.elsevier.com/computational-and-structural-biotechnology-journal

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