Elucidation of the role of claudin on the tight junction mechanism

2016 Fiscal Year Final Research Report

• Project/Area Number: 25840028
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Shinoda Takehiro 国立研究開発法人理化学研究所, ライフサイエンス技術基盤研究センター, 研究員 (10597868)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 密着結合 / 大腸菌無細胞タンパク質合成技術 / 膜タンパク質 / X線結晶構造解析

Outline of Final Research Achievements

In this study, we determined the crystal structure of the complex of human claudin-4 which is a main component of tight junction strand of the intestinal epithelial barriers with the C-terminal domain of the Clostridium perfringens enterotoxin (C-CPE) at 3.5-angstrom resolution.
The complex structure of claudin-4 and C-CPE revealed the details about the interaction between them and the differences with the off-target claudin. Moreover, a comparison of the present C-CPE-bound structure of claudin-4 with the enterotoxin-free claudin-15 structure revealed sophisticated C-CPE-induced conformation changes of the extracellular segments, induced upon the foundation of the rigid four-transmembrane-helix bundle structure. These conformation changes provide a mechanistic model for the disruption of the lateral assembly of claudin molecules.

Free Research Field

分子生物学