The cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli
The cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli
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DOI：
10.1016/s0041-0101(01)00154-4
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发表时间：
2001-11-01
期刊：
影响因子：
2.8
通讯作者：
Boquet, P
中科院分区：
文献类型：
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作者：
Boquet, P
来自尿路致病性大肠杆菌的细胞毒性坏死性因子1是rho - gtpases激活细菌毒素的范例。CNF1是一种分子量为108 kDa的a - b蛋白毒素，分为三个结构域，涉及中毒过程的三个步骤。n端结构域包含细胞受体功能，并与尚未鉴定的细胞受体具有高亲和力。毒素结合后，通过内吞作用将其内化，并转运到晚期内体。中间毒素结构域包含两个疏水螺旋，允许毒素在后期核内体酸化时跨膜易位。最后，CNF1的羧基末端结构域是一种酶，它可以脱酰胺Rho- gtp结合蛋白（Rho， Rac和Cdc42）谷氨酰胺63 （Rho）或谷氨酰胺61 （Rac和Cdc42）。谷氨酰胺63/61的脱酰胺阻断了GTP的内在或GTP酶激活蛋白（GAP）诱导的水解，导致GTP酶的永久激活。通过CNF1激活Rho gtpase诱导细胞肌动蛋白骨架的深刻重组。由于其在Rho GTPases上的特性，CNF1是迄今为止细胞生物学研究的宝贵工具。(C) 2001年Elsevier Science Ltd.出版
The cytotoxic necrotizing factor 1, from uropathogenic Escherichia coli, is the paradigm of Rho-GTPases-activating bacterial toxins. CNF1 is a MW 108 kDa A-B protein toxin divided into three domains which are implicated in the three steps of the intoxication process. The N-terminal domain contains the cell receptor function and binds with high affinity to a cell receptor not yet identified. Binding of the toxin is followed by its internalization by endocytosis and its transport into late endosomes. The middle toxin domain contains two hydophobic helices which allow translocation of the toxin across the membrane upon acidification in late endosomes. Finally the carboxy-terminal domain of CNF1 is an enzyme which deamidates Rho-GTP-binding proteins (Rho, Rac and Cdc42) glutamine 63 (for Rho) or glutamine 61 (for Rac and Cdc42). Deamidation of glutamine 63/61 blocks the intrinsic or the GTPase activating protein (GAP)-induced hydrolysis of GTP leading to the permanent activation of the GTPase. Activation of Rho GTPases by CNF1 induces a profound reorganization of the cell actin cytoskeleton. By its properties on Rho GTPases CNF1 is to date an invaluable tool for cell biology studies. (C) 2001 Published by Elsevier Science Ltd.