TITLE

The structure of a reduced form of OxyR from Neisseria meningitidis

AUTHOR(S)
Sainsbury, Sarah; Ren, Jingshan; Nettleship, Joanne E.; Saunders, Nigel J.; Stuart, David I.; Owens, Raymond J.
PUB. DATE
January 2010
SOURCE
BMC Structural Biology;2010, Vol. 10, p10
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Survival of the human pathogen, Neisseria meningitidis, requires an effective response to oxidative stress resulting from the release of hydrogen peroxide by cells of the human immune system. In N. meningitidis, expression of catalase, which is responsible for detoxifying hydrogen peroxide, is controlled by OxyR, a redox responsive LysR-type regulator. OxyR responds directly to intracellular hydrogen peroxide through the reversible formation of a disulphide bond between C199 and C208 in the regulatory domain of the protein. Results: We report the first crystal structure of the regulatory domain of an OxyR protein (NMB0173 from N. meningitidis) in the reduced state i.e. with cysteines at positions 199 and 208. The protein was crystallized under reducing conditions and the structure determined to a resolution of 2.4 Ã…. The overall fold of the Neisseria OxyR shows a high degree of similarity to the structure of a C199S mutant OxyR from E. coli, which cannot form the redox sensitive disulphide. In the neisserial structure, C199 is located at the start of helix a3, separated by 18 Ã… from C208, which is positioned between helices a3 and a4. In common with other LysR-type regulators, full length OxyR proteins are known to assemble into tetramers. Modelling of the full length neisserial OxyR as a tetramer indicated that C199 and C208 are located close to the dimer-dimer interface in the assembled tetramer. The formation of the C199-C208 disulphide may thus affect the quaternary structure of the protein. Conclusion: Given the high level of structural similarity between OxyR from N. meningitidis and E. coli, we conclude that the redox response mechanism is likely to be similar in both species, involving the reversible formation of a disulphide between C199-C208. Modelling suggests that disulphide formation would directly affect the interface between regulatory domains in an OxyR tetramer which in turn may lead to an alteration in the spacing/orientation of the DNA-binding domains and hence the interaction of OxyR with its DNA binding sites.
ACCESSION #
52040005

 

Related Articles

  • Identification of a novel anti-σE factor in Neisseria meningitidis. Hopman, Carla Th. P.; Speijer, Dave; van der Ende, Arie; Pannekoek, Yvonne // BMC Microbiology;2010, Vol. 10, p164 

    Background: Fine tuning expression of genes is a prerequisite for the strictly human pathogen Neisseria meningitidis to survive hostile growth conditions and establish disease. Many bacterial species respond to stress by using alternative s factors which, in complex with RNA polymerase...

  • Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease. Davila, Sonia; Wright, Victoria J.; Chiea Chuen Khor; Kar Seng Sim; Binder, Alexander; Breunis, Willemijn B.; Inwald, David; Nadel, Simon; Betts, Helen; Carrol, Enitan D.; de Groot, Ronald; Hermans, Peter W. M.; Hazelzet, Jan; Emonts, Marieke; Chui Chin Lim; Kuijpers, Taco W.; Martinon-Torres, Federico; Salas, Antonio; Zenz, Werner; Levin, Michael // Nature Genetics;Sep2010, Vol. 42 Issue 9, p772 

    Meningococcal disease is an infection caused by Neisseria meningitidis. Genetic factors contribute to host susceptibility and progression to disease, but the genes responsible for disease development are largely unknown. We report here a genome-wide association study for host susceptibility to...

  • Investigation of the basis of virulence in serotype A strains of Cryptococcus neoformans from apparently immunocompetent individuals. D’Souza, Cletus A.; Hagen, Ferry; Boekhout, Teun; Cox, Gary M.; Heitman, Joseph // Current Genetics;Aug2004, Vol. 46 Issue 2, p92 

    Cryptococcus neoformans serotype A strains commonly infect immunocompromised patients to cause fungal meningitis. To understand the basis of serotype A cryptococcal infections in apparently immunocompetent patients, we tested two hypotheses: the strains were naturally occurring hypervirulent...

  • IMMUNOLOGICAL EVALUATION OF TWO DIFFERENT CONSTRUCTS OF DENGUE-1-P64k CHIMERIC PROTEINS. Hermida, Lisset; Rodríguez, Rayner; Lazo, Laura; Bernardo, Lídice; Silva, Ricardo; Zulueta, Aída; López, Carlos; Martín, Jorge; Valdés, Iris; Del Rosario, Delfina; Chinea, Glay; Guzmán, Guadalupe; Guillén, Gerardo // Revista VacciMonitor (Vacunología y Temas Afines);Oct2002, Vol. 11 Issue 4, p1 

    The Dengue viruses (DEN) are human pathogens that cause a disease called Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS). It has been demonstrated that the E recombinant protein from DEN is capable to elicit high neutralizing antibodies and a protective immunity in mice. In this...

  • Progressive Decrease in the Potential Usefulness of Meningococcal Serogroup B Vaccine (4CMenB, Bexsero®) in Gipuzkoa, Northern Spain. Pérez-Trallero, Emilio; Esnal, Olatz; Marimón, José M. // PLoS ONE;Dec2014, Vol. 9 Issue 12, p1 

    The effectiveness of a vaccine is determined not only by the immunogenicity of its components, but especially by how widely it covers the disease-causing strains circulating in a given region. Because vaccine coverage varies over time, this study aimed to detect possible changes that could...

  • Meningitis bacteria temperature responsive.  // Laboratory News;Nov2013, p3 

    The article reports on the results of a study conducted by the University of Oxford and Imperial College London in England which show that the bacteria Neisseria meningitides, responsible for meningitis and sepsis, use their natural temporary sensors to avoid detection by the immune system.

  • Resistance proteins: scouts of the plant innate immune system. Wladimir Tameling; Frank Takken // European Journal of Plant Pathology;Jul2008, Vol. 121 Issue 3, p243 

    Abstract  Recognition of non-self in plants is mediated by specialised receptors that upon pathogen perception trigger induction of host defence responses. Primary, or basal, defence is mainly triggered by trans-membrane receptors that recognise conserved molecules released by a variety of...

  • Determining the Repertoire of Immunodominant Proteins via Whole-Genome Amplification of Intracellular Pathogens. Dark, Michael J.; Lundgren, Anna M.; Barbet, Anthony F. // PLoS ONE;Apr2012, Vol. 7 Issue 4, p1 

    Culturing many obligate intracellular bacteria is difficult or impossible. However, these organisms have numerous adaptations allowing for infection persistence and immune system evasion, making them some of the most interesting to study. Recent advancements in genome sequencing, pyrosequencing...

  • Determining the Repertoire of Immunodominant Proteins via Whole-Genome Amplification of Intracellular Pathogens. Dark, Michael J.; Lundgren, Anna M.; Barbet, Anthony F. // PLoS ONE;Apr2012, Vol. 7 Issue 4, p1 

    Culturing many obligate intracellular bacteria is difficult or impossible. However, these organisms have numerous adaptations allowing for infection persistence and immune system evasion, making them some of the most interesting to study. Recent advancements in genome sequencing, pyrosequencing...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

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

Try another library?
Sign out of this library

Other Topics