Journal of Proteomics & Bioinformatics
Open Access
ISSN: 0974-276X
ISSN: 0974-276X
Toshiya Senda
High Energy Accelerator Research Organization (KEK), Japan
Scientific Tracks Abstracts: J Proteomics Bioinform
Helicobacter pylori, a Gram-negative bacterium that colonizes the human gastric mucosa is recognized as a major risk factor for gastric diseases, such as peptic ulcers and gastric carcinomas. H. pylori delivers an effector protein CagA into gastric epithelial cells and the EPIYA and CM segments in the C-terminal intrinsically disordered (ID) region of CagA (CagA-C) promiscuously interact with cellular signaling molecules, such as SHP2 and PAR1b, to deregulate these signaling proteins. To analyze the structure and function of a large protein complex formed by CagA, SHP2, and PAR1b, we started a structural biology study of the CagA-SHP2-PAR1b complex. Since our group already determined the crystal structure of the N-terminal structured region of CagA (CagA-N), we are working on structure and function of CagA-C. Our biochemical analysis suggested that the CBS segment in the CagA-C region interacts with the NBS segment in CagA-N, forming a four-�?±-helix bundle structure and the CagA-C region adopts a lariat-loop like structure. Interestingly, mutations in the NBS and CBS segments caused a reduced biological activity of CagA (humminbird-inducing ability in AGS cells). For further understanding of the structure-function relationship of CagA-C, we have confirmed the existence of the lariat-loop like structure. In addition, we have obtained some structural information of the CagA-C region and its interaction with SHP2. We will discuss the structural characteristics of CagA-C and its relationship to the biological activities.
Toshiya Senda has completed his PhD from Nagaoka University of Technology, Niigata, Japan in 1995. He was a Research Associate in Nagaoka University of Technology (1995-2001) and a Senior Researcher in Institute of Advanced Industrial Science and Technology (2001-2012). Presently, he is the Director/Professor of Structural Biology Research Center of High Energy Accelerator Research Organization in Japan. He was awarded the CrSJ (Crystallographic Society of Japan) Award in 2014.
Email: toshiya.senda@kek.jp