Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan. Department of Basic Medical Science, Graduate School of Pharmaceutical Science, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
Science. 2015 Feb 13;347(6223):775-8. doi: 10.1126/science.1261833.
The C-terminal region of Clostridium perfringens enterotoxin (C-CPE) can bind to specific claudins, resulting in the disintegration of tight junctions (TJs) and an increase in the paracellular permeability across epithelial cell sheets. Here we present the structure of mammalian claudin-19 in complex with C-CPE at 3.7 Å resolution. The structure shows that C-CPE forms extensive hydrophobic and hydrophilic interactions with the two extracellular segments of claudin-19. The claudin-19/C-CPE complex shows no density of a short extracellular helix that is critical for claudins to assemble into TJ strands. The helix displacement may thus underlie C-CPE-mediated disassembly of TJs.
产气荚膜梭菌肠毒素（C-CPE）的 C 端区域可以与特定的紧密连接蛋白（claudins）结合，导致紧密连接（TJs）解体和上皮细胞片层的旁细胞通透性增加。在这里，我们以 3.7 Å 的分辨率呈现了与 C-CPE 结合的哺乳动物紧密连接蛋白 19 的结构。该结构表明，C-CPE 与紧密连接蛋白 19 的两个细胞外片段形成广泛的疏水和亲水相互作用。紧密连接蛋白 19/C-CPE 复合物没有形成对于将紧密连接蛋白组装成 TJ 链至关重要的短细胞外螺旋的密度。因此，螺旋位移可能是 C-CPE 介导的 TJ 解体的基础。
