4QQ1

Crystal structure of the isotype 1 Transferrin binding protein B (TbpB) from serogroup B Neisseria meningitidis

Summary for 4QQ1

• Entry DOI: 10.2210/pdb4qq1/pdb
• Descriptor: Transferrin-binding protein 2, CESIUM ION, GLYCEROL, ... (5 entities in total)
• Functional Keywords: vaccine candidate, transferrin receptor, iron acquisition, surface lipoprotein, host-pathogen interaction, iron piracy, transferrin binding, outer-membrane, protein binding
• Biological source: Neisseria meningitidis serogroup B
• Cellular location: Cell outer membrane ; Lipid- anchor : Q06988
• Total number of polymer chains: 3
• Total formula weight: 179713.31

Authors

Calmettes, C.,Moraes, T.F. (deposition date: 2014-06-26, release date: 2015-04-01, Last modification date: 2024-10-16)

Primary citation

Adamiak, P.,Calmettes, C.,Moraes, T.F.,Schryvers, A.B.
Patterns of structural and sequence variation within isotype lineages of the Neisseria meningitidis transferrin receptor system.
Microbiologyopen, 4:491-504, 2015

PubMed 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.

PubMed: 25800619
DOI: 10.1002/mbo3.254

Experimental method

X-RAY DIFFRACTION (3.33 Å)