Structural and functional analysis of the mechanism underlying perturbation of Csk by Helicobacter pylori virulence factor CagA

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860284
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bacteriology (including mycology)
• Research Institution: The University of Tokyo
• Principal Investigator: Hayashi Takeru 東京大学, 医学(系)研究科(研究院), 助教 (10722209)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: ピロリ菌 / CagA / 細胞内シグナル撹乱 / 構造-機能解析

Outline of Final Research Achievements

We established the experimental method for expression and purification of tyrosine-phosphorylated CagA oncoprotein from Helicobacter pylori by employing bacterial expression system. Using the purified tyrosine-phosphorylated CagA protein, we elucidated that the interaction of CagA with Csk, one of the intracellular targets of CagA, is due to direct binding and that the CagA-bound Csk is aberrantly activated. Among multiple tyrosine-phosphorylation motifs in a single CagA molecule, we identified the key motif for the interaction of CagA with Csk. Furthermore, crystal structure analysis revealed that the interaction mode of CagA-Csk complex.

Free Research Field

医歯薬学