Publication Date:
2012-02-14
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292680/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292680/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Noinaj, Nicholas -- Easley, Nicole C -- Oke, Muse -- Mizuno, Naoko -- Gumbart, James -- Boura, Evzen -- Steere, Ashley N -- Zak, Olga -- Aisen, Philip -- Tajkhorshid, Emad -- Evans, Robert W -- Gorringe, Andrew R -- Mason, Anne B -- Steven, Alasdair C -- Buchanan, Susan K -- P41 RR005969/RR/NCRR NIH HHS/ -- P41-RR05969/RR/NCRR NIH HHS/ -- R01 GM086749/GM/NIGMS NIH HHS/ -- R01-DK21739/DK/NIDDK NIH HHS/ -- R01-GM086749/GM/NIGMS NIH HHS/ -- U54 GM087519/GM/NIGMS NIH HHS/ -- U54-GM087519/GM/NIGMS NIH HHS/ -- ZIA DK036143-04/Intramural NIH HHS/ -- England -- Nature. 2012 Feb 12;483(7387):53-8. doi: 10.1038/nature10823.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22327295" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Apoproteins/chemistry/metabolism
;
Bacterial Proteins/*chemistry/metabolism/ultrastructure
;
Binding Sites
;
Biological Transport
;
Cattle
;
Crystallography, X-Ray
;
Humans
;
Iron/*metabolism
;
Mice
;
Models, Molecular
;
Molecular Dynamics Simulation
;
Neisseria/*metabolism/pathogenicity
;
Protein Conformation
;
Scattering, Small Angle
;
Species Specificity
;
Structure-Activity Relationship
;
Transferrin/chemistry/metabolism/ultrastructure
;
Transferrin-Binding Protein A/*chemistry/*metabolism/ultrastructure
;
Transferrin-Binding Protein B/*chemistry/*metabolism/ultrastructure
;
X-Ray Diffraction
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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