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J. Biol. Chem., Vol. 281, Issue 11, 7220-7227, March 17, 2006

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Solution Structure of the Immunodominant Domain of Protective Antigen GNA1870 of Neisseria meningitidis^*

Francesca Cantini, Silvana Savino, Maria Scarselli, Vega Masignani, Mariagrazia Pizza, Giacomo Romagnoli, Erwin Swennen, Daniele Veggi, Lucia Banci, and Rino Rappuoli¹

From the Centro Risonanze Magnetiche (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy and CHIRON Vaccines Research Center, Via Fiorentina, 1, 53100 Siena, Italy

GNA1870, a 28-kDa surface-exposed lipoprotein of Neisseria meningitidis recently discovered by reverse vaccinology, is one of the most potent antigens of Meningococcus and a promising candidate for a universal vaccine against a devastating disease. Previous studies of epitope mapping and genetic characterization identified residues critical for bactericidal response within the C-terminal domain of the molecule. To elucidate the conformation of protective epitopes, we used NMR spectroscopy to obtain the solution structure of the immunodominant 18-kDa C-terminal portion of GNA1870. The structure consists of an eight-stranded antiparallel -barrel overlaid by a short -helix with an unstructured N-terminal end. Residues previously shown to be important for antibody recognition were mapped on loops facing the same ridge of the molecule. The sequence similarity of GNA1870 with members of the bacterial transferrin receptor family allows one to predict the folding of this class of well known bacterial antigens, providing the basis for the rational engineering of high affinity B cell epitopes.

Received for publication, August 4, 2005 , and in revised form, December 23, 2005.

The atomic coordinates and structure factors (code 1YS5) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported by Ministero dell' Istruzione dell' Università e della Ricerca (MIUR) (Fondo per gli Investimenti della Ricerca di Base) protocol number MIUR-RBLA032ZM7 entitled "Piattaforme NMR per lo studio dell'interazione proteine-leganti di interesse farmacologico." The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: IRIS Research Ctr., Chiron srl. Via Fiorentina, 1, 53100 Siena, Italy. E-mail: rino_rappuoli{at}chiron.com.

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