Structural basis for iron piracy by pathogenic Neisseria
Nicholas Noinaj,
Nicole C. Easley,
Muse Oke,
Naoko Mizuno,
James Gumbart,
Evzen Boura,
Ashley N. Steere,
Olga Zak,
Philip Aisen,
Emad Tajkhorshid,
Robert W. Evans,
Andrew R. Gorringe,
Anne B. Mason,
Alasdair C. Steven and
Susan K. Buchanan ()
Additional contact information
Nicholas Noinaj: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health
Nicole C. Easley: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health
Muse Oke: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health
Naoko Mizuno: Laboratory of Structural Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, US National Institutes of Health
James Gumbart: Argonne National Laboratory
Evzen Boura: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health
Ashley N. Steere: University of Vermont, College of Medicine, 89 Beaumont Avenue, Burlington, Vermont 05405, USA
Olga Zak: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
Philip Aisen: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
Emad Tajkhorshid: University of Illinois at Urbana-Champaign
Robert W. Evans: Metalloprotein Research Group, School of Health Sciences and Social Care, Brunel University, Uxbridge, Middlesex UB8 3PH, UK
Andrew R. Gorringe: Health Protection Agency, Porton Down, Salisbury SP2 8NY, UK
Anne B. Mason: University of Vermont, College of Medicine, 89 Beaumont Avenue, Burlington, Vermont 05405, USA
Alasdair C. Steven: Laboratory of Structural Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, US National Institutes of Health
Susan K. Buchanan: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health
Nature, 2012, vol. 483, issue 7387, 53-58
Abstract:
Abstract Neisseria are obligate human pathogens causing bacterial meningitis, septicaemia and gonorrhoea. Neisseria require iron for survival and can extract it directly from human transferrin for transport across the outer membrane. The transport system consists of TbpA, an integral outer membrane protein, and TbpB, a co-receptor attached to the cell surface; both proteins are potentially important vaccine and therapeutic targets. Two key questions driving Neisseria research are how human transferrin is specifically targeted, and how the bacteria liberate iron from transferrin at neutral pH. To address these questions, we solved crystal structures of the TbpA–transferrin complex and of the corresponding co-receptor TbpB. We characterized the TbpB–transferrin complex by small-angle X-ray scattering and the TbpA–TbpB–transferrin complex by electron microscopy. Our studies provide a rational basis for the specificity of TbpA for human transferrin, show how TbpA promotes iron release from transferrin, and elucidate how TbpB facilitates this process.
Date: 2012
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Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:483:y:2012:i:7387:d:10.1038_nature10823
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DOI: 10.1038/nature10823
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