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Microbiologyopen. 2015 Jun;4(3):491-504. doi: 10.1002/mbo3.254. Epub 2015 Mar 19.

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

Author information

1
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
2
Department of Biochemistry, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.

Abstract

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.

KEYWORDS:

Iron acquisition; outer membrane protein; sequence variation; transferrin receptor

PMID:
25800619
PMCID:
PMC4475390
DOI:
10.1002/mbo3.254
[Indexed for MEDLINE]
Free PMC Article

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