Crystal structure of the TNF-alpha-Inducing protein (Tipalpha) from Helicobacter pylori: Insights into Its DNA-binding activity.
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.
Jang
Jun Young
JY
Department of Chemistry, Seoul National University, Korea.
Yoon
Hye-Jin
HJ
Yoon
Ji Young
JY
Kim
Hyoun Sook
HS
Lee
Sang Jae
SJ
Kim
Kyoung Hoon
KH
Kim
Do Jin
DJ
Jang
Soonmin
S
Han
Byeong-Gu
BG
Lee
Byung Il
BI
Suh
Se Won
SW
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
D001426:Bacterial Proteins; C505332:Tipalpha protein, Helicobacter pylori; D004247:DNA