3vnc

Publication Abstract from PubMed

Tipalpha (TNF-alpha-inducing protein) from Helicobacter pylori is a carcinogenic effector. Studies on this protein revealed that a homodimer linked by a pair of intermolecular disulfide bridges (Cys25-Cys25 and Cys27-Cys27) was absolutely necessary for its biological functions. The activities of Tipalpha would be abolished when both disulfide bridges were disrupted. The crystal structures of Tipalpha reported to date, however, were based on inactive, monomeric mutants with their N-terminal, including residues Cys25 and Cys27, truncated. Here we report the crystal structure of H. pylori Tipalpha protein, TipalphaN(25), at 2.2A resolution, in which Cys25 and Cys27 form a pair of inter-chain disulfide bridges linking an active dimer. The disulfide bridges exhibit structural flexibility in the present structure. A series of structure-based mutagenesis, biochemical assays and molecular dynamic simulations on DNA-Tipalpha interactions reveal that Tipalpha utilizes the dimeric interface as the DNA-binding site and that residues His60, Arg77 and Arg81 located at the interface are crucial for DNA binding. Tipalpha could bind to one ssDNA, two ssDNA or one dsDNA in experiments, respectively, in the native or mutant states. The unique DNA-binding activities of Tipalpha indicate that the intrinsic flexible nature of disulfide bridges could endow certain elasticity to the Tipalpha dimer for its unique bioactivities. The results shed light on the possible structural mechanism for the functional performances of Tipalpha.

Crystal Structure of TNF-alpha-Inducing Protein from Helicobacter Pylori in Active Form Reveals the Intrinsic Molecular Flexibility for Unique DNA-Binding.,Gao M, Li D, Hu Y, Zhang Y, Zou Q, Wang DC PLoS One. 2012;7(7):e41871. Epub 2012 Jul 31. PMID:22860022^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.