title: Structural basis for the Helicobacter pylori-carcinogenic TNF-alpha-inducing protein.
abstract: Stomach cancer is strongly associated with infection by Helicobacter pylori. In 2005, we identified a new H. pylori gene encoding a TNF-alpha inducing protein (Tipalpha) that acts as a carcinogenic factor. Tipalpha is secreted from H. pylori as a homodimer whose subunits are linked by disulfide bonds. We also characterized a Tipalpha deletion mutant (del-Tipalpha) that lacks the N-terminal six amino acid residues (LQACTC), including two cysteines (C5 and C7) that form disulfide bonds, but nonetheless shows a weak ability to induce TNF-alpha expression. Here we report that del-Tipalpha has a novel elongated structure containing a 40-A-long alpha helix, and forms a heart-shaped homodimer via non-covalent bonds. Moreover, their circular dichroism spectra strongly suggest that the structures of the del-Tipalpha and Tipalpha homodimers are very similar. del-Tipalpha's unique mode of dimer formation provides important insight into protein-protein interactions and into the mechanism underlying the carcinogenicity of H. pylori infection.
authors: Institute for Health Sciences, Tokushima Bunri University, Yamashiro-Cho, Tokushima 770-8514, Japan. tsuge@tokushima.bunri-u.ac.jp
authors: Hideaki
authors: H
authors: Tsuge
authors: Toshiharu
authors: T
authors: Tsurumura
authors: Hiroko
authors: H
authors: Utsunomiya
authors: Daisuke
authors: D
authors: Kise
authors: Takashi
authors: T
authors: Kuzuhara
authors: Tatsuro
authors: T
authors: Watanabe
authors: Hirota
authors: H
authors: Fujiki
authors: Masami
authors: M
authors: Suganuma
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D016480:Helicobacter pylori / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017384:Sequence Deletion; D013274:Stomach Neoplasms / Q000378:metabolism / Q000382:microbiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C505332:Tipalpha protein, Helicobacter pylori; D014409:Tumor Necrosis Factor-alpha