Michael Smith Building, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, United Kingdom.
PLoS One. 2013;8(2):e56746. doi: 10.1371/journal.pone.0056746. Epub 2013 Feb 15.
FrpB is an outer membrane transporter from Neisseria meningitidis, the causative agent of meningococcal meningitis. It is a member of the TonB-dependent transporter (TBDT) family and is responsible for iron uptake into the periplasm. FrpB is subject to a high degree of antigenic variation, principally through a region of hypervariable sequence exposed at the cell surface. From the crystal structures of two FrpB antigenic variants, we identify a bound ferric ion within the structure which induces structural changes on binding which are consistent with it being the transported substrate. Binding experiments, followed by elemental analysis, verified that FrpB binds Fe(3+) with high affinity. EPR spectra of the bound Fe(3+) ion confirmed that its chemical environment was consistent with that observed in the crystal structure. Fe(3+) binding was reduced or abolished on mutation of the Fe(3+)-chelating residues. FrpB orthologs were identified in other Gram-negative bacteria which showed absolute conservation of the coordinating residues, suggesting the existence of a specific TBDT sub-family dedicated to the transport of Fe(3+). The region of antigenic hypervariability lies in a separate, external sub-domain, whose structure is conserved in both the F3-3 and F5-1 variants, despite their sequence divergence. We conclude that the antigenic sub-domain has arisen separately as a result of immune selection pressure to distract the immune response from the primary transport function. This would enable FrpB to function as a transporter independently of antibody binding, by using the antigenic sub-domain as a 'molecular decoy' to distract immune surveillance.
FrpB 是脑膜炎奈瑟菌（导致脑膜炎球菌性脑膜炎的病原体）的外膜转运蛋白。它是 TonB 依赖性转运体（TBDT）家族的成员，负责将铁摄取到周质中。FrpB 高度具有抗原变异性，主要通过暴露在细胞表面的超变序列区域。从两种 FrpB 抗原变异体的晶体结构中，我们在结构中鉴定出一个结合的三价铁离子，该离子在结合时诱导结构变化，与它作为转运底物一致。结合实验后进行元素分析，验证了 FrpB 与 Fe(3+) 具有高亲和力结合。结合态 Fe(3+) 的 EPR 光谱证实其化学环境与晶体结构中观察到的一致。Fe(3+)结合在螯合 Fe(3+) 残基的突变中减少或消除。在其他革兰氏阴性菌中鉴定出 FrpB 的同源物，其配位残基绝对保守，表明存在一个专门用于转运 Fe(3+)的特定 TBDT 亚家族。抗原高变异性的区域位于一个单独的外部亚结构域中，尽管 F3-3 和 F5-1 变体的序列存在差异，但它们的结构在这两个变体中是保守的。我们得出结论，抗原亚结构域是由于免疫选择压力而独立出现的，以将免疫反应从主要的转运功能中转移开。这将使 FrpB 能够独立于抗体结合而发挥转运体的作用，通过将抗原亚结构域用作“分子诱饵”来分散免疫监视。
