Use of a Molecular Decoy to Segregate Transport from Antigenicity in the FrpB Iron Transporter from Neisseria meningitidis

• DOI: 10.1371/journal.pone.0056746
• Publication Date: 2013-02-15T23:07:50Z
• Authors: Muhammad Saleem; Stephen M. Prince; Stephen E. J. Rigby; Muhammad Imran; Hema Patel; Hannah Chan; Holly Sanders; Martin C. J. Maiden; Ian M. Feavers; Jeremy P. Derrick
• Keywords: Hypervariable region; Antigenic variation; Antigenicity

FrpB is an outer membrane transporter from Neisseria meningitidis, the causative agent of meningococcal meningitis. It a member TonB-dependent (TBDT) family and responsible for iron uptake into periplasm. subject to high degree antigenic variation, principally through region hypervariable sequence exposed at cell surface. From crystal structures two variants, we identify bound ferric ion within structure which induces structural changes on binding are consistent with it being transported substrate. Binding experiments, followed by elemental analysis, verified that binds Fe3+ affinity. EPR spectra confirmed its chemical environment was observed in structure. reduced or abolished mutation Fe3+-chelating residues. orthologs were identified other Gram-negative bacteria showed absolute conservation coordinating residues, suggesting existence specific TBDT sub-family dedicated transport Fe3+. The hypervariability lies separate, external sub-domain, whose conserved both F3-3 F5-1 despite their divergence. We conclude sub-domain has arisen separately as result immune selection pressure distract response primary function. This would enable function independently antibody binding, using 'molecular decoy' surveillance.