Role of Tyr306 in the C-terminal fragment of Clostridium perfringens enterotoxin for modulation of tight junction
Role of Tyr306 in the C-terminal fragment of Clostridium perfringens enterotoxin for modulation of tight junction
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DOI：
10.1016/j.bcp.2006.11.013
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发表时间：
2007-03-15
影响因子：
5.8
通讯作者：
Watanabe, Yoshiteru
中科院分区：
文献类型：
--
作者：
Ebihara, Chiaki;Kondoh, Masuo;Watanabe, Yoshiteru
我们先前报道了产气荚膜梭菌肠毒素（C-CPE）的C末端片段是一种新型的吸收促进剂，其与claudin-4相互作用，并且C-CPE的Tyr 306在C-CPE调节紧密连接屏障的能力中起作用。为了研究Tyr 306对C-CPE活性的影响，我们制备了Tyr 306分别被Trp（Y306 W）、Phe（Y306 F）和Lys（Y306 K）取代的C-CPE突变体。我们发现C-CPE的Y306 W和Y306 F突变体具有紧密连接蛋白-4结合亲和力和对紧密连接屏障功能的影响，而Y306 K突变体的这两种性质都大大降低。最后，Y306 K而不是Y306 F和Y306 W突变体具有降低的能力，以提高在大鼠空肠中的吸收。这些结果表明，芳香族和疏水性，而不是氢键的潜力，Tyr 306参与C-CPE与claudin-4的相互作用，并在由C-CPE的紧密连接屏障功能的调制。(c)2006年爱思唯尔公司All rights reserved.
We previously reported that the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) is a novel type of absorption enhancer that interacts with claudin-4 and that Tyr306 of C-CPE plays a role in ability of C-CPE to modulate barrier of tight junctions. In the current study, to investigate effects of Tyr306 on the C-CPE activity, we prepared some C-CPE mutants substituted Tyr306 with Trp (Y306W), Phe (Y306F) and Lys (Y306K). We found that Y306W and Y306F mutants of C-CPE had claudin-4 binding affinities and effects on the barrier function of tight junctions, whereas both of these properties were greatly reduced with the Y306K mutant. Finally, the Y306K but not the Y306F and Y306W mutants had reduced abilities to enhance absorption in rat jejunum. These results indicate that aromatic and hydrophobic properties, not hydrogen bonding potential, of Tyr306 are involved in the interaction of C-CPE with claudin-4 and in the modulation of the tight junction barrier function by C-CPE. (c) 2006 Elsevier Inc. All rights reserved.