Tsuge Hideaki, Tsurumura Toshiharu, Utsunomiya Hiroko, Kise Daisuke, Kuzuhara Takashi, Watanabe Tatsuro, Fujiki Hirota, Suganuma Masami
Institute for Health Sciences, Tokushima Bunri University, Yamashiro-Cho, Tokushima 770-8514, Japan.
Biochem Biophys Res Commun. 2009 Oct 16;388(2):193-8. doi: 10.1016/j.bbrc.2009.07.121. Epub 2009 Jul 28.
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.
胃癌与幽门螺杆菌感染密切相关。2005年，我们鉴定出一种新的幽门螺杆菌基因，该基因编码一种作为致癌因子的肿瘤坏死因子-α诱导蛋白（Tipalpha）。Tipalpha以同源二聚体形式从幽门螺杆菌分泌出来，其亚基通过二硫键相连。我们还对一种Tipalpha缺失突变体（del-Tipalpha）进行了表征，该突变体缺少N端的六个氨基酸残基（LQACTC），包括形成二硫键的两个半胱氨酸（C5和C7），但仍表现出较弱的诱导肿瘤坏死因子-α表达的能力。在此我们报告，del-Tipalpha具有一种新颖的细长结构，包含一个40埃长的α螺旋，并通过非共价键形成心形同源二聚体。此外，它们的圆二色光谱强烈表明del-Tipalpha和Tipalpha同源二聚体的结构非常相似。del-Tipalpha独特的二聚体形成模式为蛋白质-蛋白质相互作用以及幽门螺杆菌感染致癌性的潜在机制提供了重要见解。
