Delineating the regions of human transferrin involved in interactions with transferrin binding protein B from Neisseria meningitidis

Molecular Microbiology
Jessmi M L LingA B Schryvers

Abstract

Pathogenic bacteria in the Neisseriaceae possess a surface receptor mediating iron acquisition from human transferrin (hTf) that consists of a transmembrane iron transporter (TbpA) and a surface-exposed lipoprotein (TbpB). In this study, we used hydrogen/deuterium exchange coupled to mass spectrometry (H/DX-MS) to elucidate the effects on hTf by interaction with TbpB or derivatives of TbpB. An overall conserved interaction was observed between hTf and full-length or N-lobe TbpB from Neisseria meningitidis strains B16B6 or M982 that represent two distinct subtypes of TbpB. Changes were observed exclusively in the C-lobe of hTf and were caused by the interaction with the N-lobe of TbpB. Regions localized to the 'lip' of the C1 and C2 domains that flank the interdomain cleft represent sites of direct contact with TbpB whereas the peptides within the interdomain cleft that encompass iron binding ligands are inaccessible in the closed (holo) conformation. Although substantial domain separation upon binding TbpB cannot be excluded by the H/DX-MS data, the preferred model of interaction involves binding hTf C-lobe in the closed conformation. Alternate explanations are provided for the substantial protection from deuteration of the pep...Continue Reading

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Citations

Feb 22, 2012·Nature Structural & Molecular Biology·Charles CalmettesTrevor F Moraes
Feb 8, 2011·The Journal of Biological Chemistry·Charles CalmettesTrevor F Moraes
Nov 10, 2011·The Journal of Biological Chemistry·Xue YangAnthony B Schryvers
Apr 14, 2011·The Journal of Biological Chemistry·Leslie P SilvaDavid C Schriemer
Dec 1, 2012·Molecular & Cellular Proteomics : MCP·Kyle M BurnsDavid C Schriemer
Sep 22, 2011·Biochimica Et Biophysica Acta·Claire J Parker SiburtAlvin L Crumbliss
Mar 4, 2017·PLoS Pathogens·Nicholas K H OstanAnthony B Schryvers
Oct 3, 2020·Protein and Peptide Letters·Thirunavukkarasu Sivaraman
May 30, 2015·Analytical Chemistry·Sean R MarcsisinJohn R Engen

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