title: Structural insight into the lactoferrin receptors from pathogenic Neisseria.
abstract: Neisseria are pathogenic bacteria that cause gonorrhea, septicemia, and meningitis. Like other pathogenic bacteria, Neisseria must acquire iron for survival from their local environment within the human host. Instead of secreting siderophores to scavenge iron, Neisseria steal iron from human iron binding proteins such as hemoglobin, transferrin and lactoferrin for survival. Recently we reported the crystal structures of the Neisseria meningitidis transferrin receptors TbpA and TbpB, as well as the structures of apo and holo human transferrin. We also analyzed these proteins using small angle X-ray scattering and electron microscopy to provide the molecular details explaining how Neisseria are able to interact with and extract iron from transferrin. Here, we utilize the structural reports, as well as the recently reported structure of the N-lobe of LbpB from Moraxella bovis, to assemble improved 3D homology models for the neisserial lactoferrin import receptors LbpA and LbpB, both of which are important vaccine targets against N. meningitidis. We then analyzed these models to gain structural insights into the lactoferrin-iron import system and form a mechanistic model fashioned in parallel to the homologous transferrin-iron import system.
authors: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States.
authors: Nicholas
authors: N
authors: Noinaj
authors: Cynthia Nau
authors: CN
authors: Cornelissen
authors: Susan K
authors: SK
authors: Buchanan
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D007501:Iron / Q000378:metabolism; D008969:Molecular Sequence Data; D016955:Moraxella bovis / Q000378:metabolism; D009345:Neisseria meningitidis / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism*; D017385:Sequence Homology; D017386:Sequence Homology, Amino Acid; D014168:Transferrin / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C112566:LBPA protein, Neisseria meningitidis; D011956:Receptors, Cell Surface; D014168:Transferrin; C038340:lactoferrin receptors; D007501:Iron
keywords: Gonorrhoeae; Iron acquisition; Lactoferrin; Neisseria meningitidis; TonB; Transferrin