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Patterns of structural and sequence variation within isotype lineages of the Neisseria meningitidis transferrin receptor system

Neisseria meningitidis inhabits the human upper respiratory tract and is an important cause of sepsis and meningitis. A surface receptor comprised of transferrin-binding proteins A and B (TbpA and TbpB), is responsible for acquiring iron from host transferrin. Sequence and immunological diversity di...

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Autores principales: Adamiak, Paul, Calmettes, Charles, Moraes, Trevor F, Schryvers, Anthony B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4475390/
https://www.ncbi.nlm.nih.gov/pubmed/25800619
http://dx.doi.org/10.1002/mbo3.254
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author Adamiak, Paul
Calmettes, Charles
Moraes, Trevor F
Schryvers, Anthony B
author_facet Adamiak, Paul
Calmettes, Charles
Moraes, Trevor F
Schryvers, Anthony B
author_sort Adamiak, Paul
collection PubMed
description Neisseria meningitidis inhabits the human upper respiratory tract and is an important cause of sepsis and meningitis. A surface receptor comprised of transferrin-binding proteins A and B (TbpA and TbpB), is responsible for acquiring iron from host transferrin. Sequence and immunological diversity divides TbpBs into two distinct lineages; isotype I and isotype II. Two representative isotype I and II strains, B16B6 and M982, differ in their dependence on TbpB for in vitro growth on exogenous transferrin. The crystal structure of TbpB and a structural model for TbpA from the representative isotype I N. meningitidis strain B16B6 were obtained. The structures were integrated with a comprehensive analysis of the sequence diversity of these proteins to probe for potential functional differences. A distinct isotype I TbpA was identified that co-varied with TbpB and lacked sequence in the region for the loop 3 α-helix that is proposed to be involved in iron removal from transferrin. The tightly associated isotype I TbpBs had a distinct anchor peptide region, a distinct, smaller linker region between the lobes and lacked the large loops in the isotype II C-lobe. Sequences of the intact TbpB, the TbpB N-lobe, the TbpB C-lobe, and TbpA were subjected to phylogenetic analyses. The phylogenetic clustering of TbpA and the TbpB C-lobe were similar with two main branches comprising the isotype 1 and isotype 2 TbpBs, possibly suggesting an association between TbpA and the TbpB C-lobe. The intact TbpB and TbpB N-lobe had 4 main branches, one consisting of the isotype 1 TbpBs. One isotype 2 TbpB cluster appeared to consist of isotype 1 N-lobe sequences and isotype 2 C-lobe sequences, indicating the swapping of N-lobes and C-lobes. Our findings should inform future studies on the interaction between TbpB and TbpA and the process of iron acquisition.
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spelling pubmed-44753902015-06-26 Patterns of structural and sequence variation within isotype lineages of the Neisseria meningitidis transferrin receptor system Adamiak, Paul Calmettes, Charles Moraes, Trevor F Schryvers, Anthony B Microbiologyopen Original Research Neisseria meningitidis inhabits the human upper respiratory tract and is an important cause of sepsis and meningitis. A surface receptor comprised of transferrin-binding proteins A and B (TbpA and TbpB), is responsible for acquiring iron from host transferrin. Sequence and immunological diversity divides TbpBs into two distinct lineages; isotype I and isotype II. Two representative isotype I and II strains, B16B6 and M982, differ in their dependence on TbpB for in vitro growth on exogenous transferrin. The crystal structure of TbpB and a structural model for TbpA from the representative isotype I N. meningitidis strain B16B6 were obtained. The structures were integrated with a comprehensive analysis of the sequence diversity of these proteins to probe for potential functional differences. A distinct isotype I TbpA was identified that co-varied with TbpB and lacked sequence in the region for the loop 3 α-helix that is proposed to be involved in iron removal from transferrin. The tightly associated isotype I TbpBs had a distinct anchor peptide region, a distinct, smaller linker region between the lobes and lacked the large loops in the isotype II C-lobe. Sequences of the intact TbpB, the TbpB N-lobe, the TbpB C-lobe, and TbpA were subjected to phylogenetic analyses. The phylogenetic clustering of TbpA and the TbpB C-lobe were similar with two main branches comprising the isotype 1 and isotype 2 TbpBs, possibly suggesting an association between TbpA and the TbpB C-lobe. The intact TbpB and TbpB N-lobe had 4 main branches, one consisting of the isotype 1 TbpBs. One isotype 2 TbpB cluster appeared to consist of isotype 1 N-lobe sequences and isotype 2 C-lobe sequences, indicating the swapping of N-lobes and C-lobes. Our findings should inform future studies on the interaction between TbpB and TbpA and the process of iron acquisition. BlackWell Publishing Ltd 2015-06 2015-03-19 /pmc/articles/PMC4475390/ /pubmed/25800619 http://dx.doi.org/10.1002/mbo3.254 Text en © 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Adamiak, Paul
Calmettes, Charles
Moraes, Trevor F
Schryvers, Anthony B
Patterns of structural and sequence variation within isotype lineages of the Neisseria meningitidis transferrin receptor system
title Patterns of structural and sequence variation within isotype lineages of the Neisseria meningitidis transferrin receptor system
title_full Patterns of structural and sequence variation within isotype lineages of the Neisseria meningitidis transferrin receptor system
title_fullStr Patterns of structural and sequence variation within isotype lineages of the Neisseria meningitidis transferrin receptor system
title_full_unstemmed Patterns of structural and sequence variation within isotype lineages of the Neisseria meningitidis transferrin receptor system
title_short Patterns of structural and sequence variation within isotype lineages of the Neisseria meningitidis transferrin receptor system
title_sort patterns of structural and sequence variation within isotype lineages of the neisseria meningitidis transferrin receptor system
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4475390/
https://www.ncbi.nlm.nih.gov/pubmed/25800619
http://dx.doi.org/10.1002/mbo3.254
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