The molecular mechanism of Zinc acquisition by the neisserial outer-membrane transporter ZnuD
Charles Calmettes,
Christopher Ing,
Carolyn M. Buckwalter,
Majida El Bakkouri,
Christine Chieh-Lin Lai,
Anastassia Pogoutse,
Scott D. Gray-Owen,
Régis Pomès and
Trevor F. Moraes ()
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Charles Calmettes: University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada
Christopher Ing: University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada
Carolyn M. Buckwalter: University of Toronto
Majida El Bakkouri: Structural Genomic Consortium, University of Toronto
Christine Chieh-Lin Lai: University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada
Anastassia Pogoutse: University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada
Scott D. Gray-Owen: University of Toronto
Régis Pomès: University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada
Trevor F. Moraes: University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada
Nature Communications, 2015, vol. 6, issue 1, 1-11
Abstract:
Abstract Invading bacteria from the Neisseriaceae, Acinetobacteriaceae, Bordetellaceae and Moraxellaceae families express the conserved outer-membrane zinc transporter zinc-uptake component D (ZnuD) to overcome nutritional restriction imposed by the host organism during infection. Here we demonstrate that ZnuD is required for efficient systemic infections by the causative agent of bacterial meningitis, Neisseria meningitidis, in a mouse model. We also combine X-ray crystallography and molecular dynamics simulations to gain insight into the mechanism of zinc recognition and transport across the bacterial outer-membrane by ZnuD. Because ZnuD is also considered a promising vaccine candidate against N. meningitidis, we use several ZnuD structural intermediates to map potential antigenic epitopes, and propose a mechanism by which ZnuD can maintain high sequence conservation yet avoid immune recognition by altering the conformation of surface-exposed loops.
Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8996
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DOI: 10.1038/ncomms8996
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