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

Saleem, Muhammad; Prince, Stephen M.; Rigby, Stephen E. J.; Imran, Muhammad; Patel, Hema; Chan, Hannah; Sanders, Holly; Maiden, Martin C. J.; Feavers, Ian M.; Derrick, Jeremy P.
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
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 Fe3+ with high affinity. EPR spectra of the bound Fe3+ ion confirmed that its chemical environment was consistent with that observed in the crystal structure. Fe3+ binding was reduced or abolished on mutation of the Fe3+-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 Fe3+. 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.


Related Articles

  • The Structure of HasB Reveals a New Class of TonB Protein Fold. Amorim, Gisele Cardoso de; Prochnicka-Chalufour, Ada; Delepelaire, Philippe; Lefèvre, Julien; Simenel, Catherine; Wandersman, Cécile; Delepierre, Muriel; Izadi-Pruneyre, Nadia // PLoS ONE;Mar2013, Vol. 8 Issue 3, p1 

    TonB is a key protein in active transport of essential nutrients like vitamin B12 and metal sources through the outer membrane transporters of Gram-negative bacteria. This inner membrane protein spans the periplasm, contacts the outer membrane receptor by its periplasmic domain and transduces...

  • Pyrophosphate-Mediated Iron Acquisition from Transferrin in Neisseria meningitidis Does Not Require TonB Activity. Biville, Francis; Brézillon, Christophe; Giorgini, Dario; Taha, Muhamed-Kheir // PLoS ONE;Oct2014, Vol. 9 Issue 10, p1 

    The ability to acquire iron from various sources has been demonstrated to be a major determinant in the pathogenesis of Neisseria meningitidis. Outside the cells, iron is bound to transferrin in serum, or to lactoferrin in mucosal secretions. Meningococci can extract iron from iron-loaded human...

  • Meningococcal Disease. Pellman, Harry // Pediatrics for Parents;2001, Vol. 19 Issue 7, p4 

    Examines the treatment of meningococcal disease in the United States. Mortally rate of affected individuals; Manners of occurrence of the disease and effects; Use of vaccine to protect against the meningococcal bacteria.

  • Mutational analysis of acylphosphatase suggests the importance of topology and contact order in protein folding. Chiti, Fabrizio; Taddei, Niccol�; White, Paul M.; Bucciantini, Monica; Magherini, Francesca; Stefani, Massimo; Dobson, Christopher M. // Nature Structural Biology;Nov99, Vol. 6 Issue 11, p1005 

    Muscle acylphosphatase (AcP) is a small protein that folds very slowly with two-state behavior. The conformational stability and the rates of folding and unfolding have been determined for a number of mutants of AcP in order to characterize the structure of the folding transition state. The...

  • Meningococcal disease, Kenya.  // Weekly Epidemiological Record;3/10/2006, Vol. 81 Issue 10, p89 

    The article reports on the total number of Meningococcal disease in Kenya. The International Coordinating Group on Vaccine Provision for Epidemic Meningitis Control has provided trivalent vaccines, chloramphenicol, rapid tests, and transport media for the affected areas.

  • Meningococcal Disease--United States, 1971.  // Clinical Pediatrics;Oct1972, Vol. 11 Issue 10, p572 

    Focuses on meningococcal disease in the U.S. in 1971. Epidemiology; Incidence rate; Attack rates.

  • Nosocomial outbreak of group C meningococcal disease. Eriksen, N.H. Riewerts; Espersen, F.; Laursen, L.; Skinhoj, P.; Hoiby, N.; Lind, I. // BMJ: British Medical Journal (International Edition);3/4/89, Vol. 298 Issue 6673, p568 

    Reports the case if group C;2a meningococcal disease within a month in a hospital. Description of the meningococci strain; Uncertainty of the risk of secondary meningococcal disease among people in the vicinity; Importance of chemoprophylaxis.

  • Does eradication of meningococcal carriage in household contacts prevent secondary cases of meningococcal disease? Stuart, James M.; Cartwright, Keith A.V.; Robinson, Priscilla M.; Noah, Norman D. // BMJ: British Medical Journal (International Edition);3/4/89, Vol. 298 Issue 6673, p569 

    Assesses the effectivity of rifampicin administration in the reduction of outbreak strains of meningococcal infection. Conduction of a community survey; Support for the practice of prescribing antibiotics; Need for family members to remain vigilant after a case of meningococcal disease.

  • Which Dutch meningococcal group C vaccination programme?  // PharmacoEconomics & Outcomes News;1/15/2005, Issue 469, p10 

    Presents information on the costs and outcomes of different vaccination strategies for invasive infections due to Neisseria meningitidis serogroup C in the Netherlands. Methods used to study the strategies; Types of strategies observed; Costs of the strategies.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics