The molecular mechanism of Zinc acquisition by the neisserial outer-membrane transporter ZnuD.
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.
Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
Charles
C
Calmettes
1] Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada [2] Program in Molecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Christopher
C
Ing
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Carolyn M
CM
Buckwalter
Structural Genomic Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
Majida
M
El Bakkouri
Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
Christine
C
Chieh-Lin Lai
Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
Anastassia
A
Pogoutse
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Scott D
0000000214773616
SD
Gray-Owen
1] Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada [2] Program in Molecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Régis
R
Pomès
Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
Trevor F
TF
Moraes
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D009345:Neisseria meningitidis / Q000378:metabolism*; D011487:Protein Conformation; D018805:Sepsis / Q000382:microbiology; D015032:Zinc / Q000378:metabolism*
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D027682:Cation Transport Proteins; C553584:ZnuD protein, Neisseria meningitidis; D015032:Zinc