title: Crystal structure of the TNF-alpha-Inducing protein (Tipalpha) from Helicobacter pylori: Insights into Its DNA-binding activity.
abstract: Helicobacter pylori infection is one of the highest risk factors for gastroduodenal diseases including gastric cancer. Tumor necrosis factor-alpha (TNF-alpha) is one of the essential cytokines for tumor promotion, and thus, an H. pylori protein that induces TNF-alpha is believed to play a significant role in gastric cancer development in humans. The HP0596 gene product of H. pylori strain 26695 was identified as the TNF-alpha-inducing protein (Tipalpha). Tipalpha is secreted from H. pylori as dimers and enters the gastric cells. It was shown to have a DNA-binding activity. Here, we have determined the crystal structure of Tipalpha from H. pylori. Its monomer consists of two structural domains ("mixed domain" and "helical domain"). Tipalpha exists as a dimer in the crystal, and the dimeric structure represents a novel scaffold for DNA binding. A positively charged surface patch formed across the two monomers of the Tipalpha dimer by the loop between helices alpha1 and alpha2 may be important in DNA binding.
authors: Department of Chemistry, Seoul National University, Korea.
authors: Jun Young
authors: JY
authors: Jang
authors: Hye-Jin
authors: HJ
authors: Yoon
authors: Ji Young
authors: JY
authors: Yoon
authors: Hyoun Sook
authors: HS
authors: Kim
authors: Sang Jae
authors: SJ
authors: Lee
authors: Kyoung Hoon
authors: KH
authors: Kim
authors: Do Jin
authors: DJ
authors: Kim
authors: Soonmin
authors: S
authors: Jang
authors: Byeong-Gu
authors: BG
authors: Han
authors: Byung Il
authors: BI
authors: Lee
authors: Se Won
authors: SW
authors: Suh
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; C505332:Tipalpha protein, Helicobacter pylori; D004247:DNA