The X-ray Structure of the N-terminal Domain of PILB from Neisseria meningitidis Reveals a Thioredoxin-fold

• Published in: Journal of molecular biology 2006-04, Vol.358 (2), p.443-454
• Main Authors: Ranaivoson, Fanomezana M., Kauffmann, Brice, Neiers, Fabrice, Wu, Junzhu, Boschi-Muller, Sandrine, Panjikar, Santosh, Aubry, André, Branlant, Guy, Favier, Frédérique
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Bacterial Proteins - chemistry; Binding Sites; Crystallography, X-Ray; Cysteine - chemistry; Cysteine - metabolism; cytochrome maturation protein; Escherichia coli; Methionine - chemistry; methionine sulfoxide reductase; Molecular Sequence Data; Neisseria gonorrhoeae; Neisseria meningitidis; Neisseria meningitidis - chemistry; Oxidoreductases - chemistry; PilB; Protein Folding; Protein Structure, Tertiary; Sequence Homology, Amino Acid; thioredoxin; Thioredoxins - chemistry; X-ray structure
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2006.02.025

The secreted form of the PilB protein was recently shown to be bound to the outer membrane of Neisseria gonorrhoeae and proposed to be involved in survival of the pathogen to the host's oxidative burst. PilB is composed of three domains. The central and the C-terminal domains display methionine sulfoxide reductase (Msr) A and B activities respectively, i.e. the ability to reduce specifically the S and the R enantiomers of the sulfoxide function of the methionine sulfoxides, which are easily formed upon oxidation of methionine residues. The N-terminal domain of PilB (Dom1 PILB) of N. meningitidis , which possesses a CXXC motif, was recently shown to recycle the oxidized forms of the PilB Msr domains in vitro, as the Escherichia coli thioredoxin (Trx) 1 does. The X-ray structure of Dom1 PILB of N. meningitidis determined here shows a Trx-fold, in agreement with the biochemical properties of Dom1 PILB. However, substantial structural differences with E. coli Trx1 exist. Dom1 PILB displays more structural homologies with the periplasmic disulfide oxidoreductases involved in cytochrome maturation pathways in bacteria. The active site of the reduced form of Dom1 PILB reveals a high level of stabilization of the N-terminal catalytic cysteine residue and a hydrophobic environment of the C-terminal recycling cysteine in the CXXC motif, consistent with the p K app values measured for Cys67 (