Crystal structure of antigen TpF1 from Treponema pallidum.

Several bacterial genomes code for pro- teins belonging to the Dps family, which includes dodecam- ers, made up of 12 identical subunits, each of them with a four-helix bundle folding similar to that of ferritins. The crystal structure of several members of the family have been determined: Dps from Escherichia coli (1DPS, 1F30, 1F33, 1JRE, 1JTS, 1L8H, 1L8I),1 Listeria Innocua Dps (1QGH, 2BJY, 2BK6, 2BKC),2,3 HP-NAP from Helicobac- ter pylori (1JI4),4 Dlp1 and Dlp2 from Bacillus anthracis (1JI5, 1JIG),5 archaeal Dps-homolog from Halobacterium salinarum (1MOJ, 1TJO),6 Dps protein from Bacillus brevis (1N1Q),7 Agrobacterium tumefaciens Dps (1O9R),8 Dps-like peroxide resistance protein from Streptococcus suis (1UMN),9 Dps from Mycobacterium smegmatis (1VEI, 1VEQ, 1UVH).10 Despite their structural similarity and the fact that most of these proteins are capable of incorporating iron in vitro, their biological function appear to differ among family members. The E. coli and the B. subtilis proteins protect DNA from oxidative damage (Dps, DNA protecting protein under starved conditions),11–13 whereas the L. innocua protein (Flp) is a true dodecameric ferritin func- tioning in iron storage.2 The FtpA protein from H. ducreyi is a structural protein of fine tangled pili.14 At variance from these Dps proteins, the H. pylori homolog HP-NAP appears to display different activities. It induces migration and activation of human neutrophils and monocytes,15 adhesion of neutrophils to endothelial cells,16 and it causes mast cell degranulation.17 HP-NAP binds to neutrophil glycosphingolipids and to mucin, a component of the stomach mucus layer.18,19 A major property of HP-NAP is that of being highly immunogenic in humans.20,21 This property is shared by a Dps-like protein, named TpF1, produced by Treponema pallidum,22–25 and therefore, we decided to undertake the determination of the crystal structure of this protein, which is presented in this report.