PMID- 19596016 OWN - NLM STAT- MEDLINE DCOM- 20090923 LR - 20160512 IS - 1089-8638 (Electronic) IS - 0022-2836 (Linking) VI - 392 IP - 1 DP - 2009 Sep 11 TI - Crystal structure of the TNF-alpha-Inducing protein (Tipalpha) from Helicobacter pylori: Insights into Its DNA-binding activity. PG - 191-7 LID - 10.1016/j.jmb.2009.07.010 [doi] AB - 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. FAU - Jang, Jun Young AU - Jang JY AD - Department of Chemistry, Seoul National University, Korea. FAU - Yoon, Hye-Jin AU - Yoon HJ FAU - Yoon, Ji Young AU - Yoon JY FAU - Kim, Hyoun Sook AU - Kim HS FAU - Lee, Sang Jae AU - Lee SJ FAU - Kim, Kyoung Hoon AU - Kim KH FAU - Kim, Do Jin AU - Kim DJ FAU - Jang, Soonmin AU - Jang S FAU - Han, Byeong-Gu AU - Han BG FAU - Lee, Byung Il AU - Lee BI FAU - Suh, Se Won AU - Suh SW LA - eng SI - PDB/3GIO PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090710 PL - Netherlands TA - J Mol Biol JT - Journal of molecular biology JID - 2985088R RN - 0 (Bacterial Proteins) RN - 0 (Tipalpha protein, Helicobacter pylori) RN - 9007-49-2 (DNA) SB - IM MH - Amino Acid Sequence MH - Bacterial Proteins/*chemistry/metabolism MH - Crystallography, X-Ray MH - DNA/metabolism MH - Dimerization MH - Models, Molecular MH - Molecular Sequence Data MH - Protein Binding MH - Protein Structure, Quaternary MH - Protein Structure, Tertiary MH - Sequence Alignment EDAT- 2009/07/15 09:00 MHDA- 2009/09/24 06:00 CRDT- 2009/07/15 09:00 PHST- 2009/03/06 00:00 [received] PHST- 2009/07/01 00:00 [revised] PHST- 2009/07/06 00:00 [accepted] PHST- 2009/07/15 09:00 [entrez] PHST- 2009/07/15 09:00 [pubmed] PHST- 2009/09/24 06:00 [medline] AID - S0022-2836(09)00836-5 [pii] AID - 10.1016/j.jmb.2009.07.010 [doi] PST - ppublish SO - J Mol Biol. 2009 Sep 11;392(1):191-7. doi: 10.1016/j.jmb.2009.07.010. Epub 2009 Jul 10.