A Novel C3-like ADP-ribosyltransferase fromStaphylococcus aureus Modifying RhoE and Rnd3*
A Novel C3-like ADP-ribosyltransferase fromStaphylococcus aureus Modifying RhoE and Rnd3*
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来自金黄色葡萄球菌的新型 C3 样 ADP-核糖基转移酶修饰 RhoE 和 Rnd3*
DOI：
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发表时间：
2001
影响因子：
4.8
通讯作者：
I. Just
中科院分区：
文献类型：
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作者：
C. Wilde;G. S. Chhatwal;G. Schmalzing;K. Aktories;I. Just
肉毒杆菌C3是adp核苷化RhoA， -B和-C的类C3转移酶家族的原型。Asn-41的adp核糖导致Rho的功能失活，反映在肌动蛋白细胞骨架的分解上。我们报告了一种新的c3样转移酶由致病性金黄色葡萄球菌菌株产生。从基因组DNA中克隆出C3Stau转移酶。在氨基酸水平上，C3Stau与C. botulinum和Clostridium limosumexoenzyme的C3的同源性分别为35%，与S. aureus的EDIN的同源性为78%。除了RhoA是其他c3样转移酶的靶标外，C3Stau修饰了RhoE和Rnd3。RhoE在Asn-44位点发生adp核糖化，相当于RhoA的Asn-41位点。RhoE和Rnd3是Rho亚家族的成员，它们缺乏内在GTPase活性，具有RhoA拮抗细胞功能。RhoE在非洲爪蟾卵母细胞中的表达证实了重组Rho蛋白的蛋白底物特异性，表明RhoE在体内也被c3stu修饰，而不是被肉毒杆菌中的C3修饰。通过产生嵌合毒素，利用肉毒杆菌C2毒素的细胞进入机制，克服了C3Stau细胞可及性差的问题。嵌合C3Stau引起的形态和细胞骨架变化与嵌合C.肉毒杆菌C3相同。c3是c3样转移酶家族的新成员，也是RhoE/Rnd修饰转移酶亚家族的原型。
Clostridium botulinum C3 is the prototype of the family of the C3-like transferases that ADP-ribosylate exclusively RhoA, -B and -C. The ADP-ribose at Asn-41 results in functional inactivation of Rho reflected by disaggregation of the actin cytoskeleton. We report on a new C3-like transferase produced by a pathogenic Staphylococcus aureus strain. The transferase designated C3Stau was cloned from the genomic DNA. At the amino acid level, C3Stau revealed an identity of 35% to C3 from C. botulinum and Clostridium limosumexoenzyme, respectively, and of 78% to EDIN from S. aureus. In addition to RhoA, which is the target of the other C3-like transferases, C3Stau modified RhoE and Rnd3. RhoE was ADP-ribosylated at Asn-44, which is equivalent to Asn-41 of RhoA. RhoE and Rnd3 are members of the Rho subfamily, which are deficient in intrinsic GTPase activity and possess a RhoA antagonistic cell function. The protein substrate specificity found with recombinant Rho proteins was corroborated by expression of RhoE in Xenopus laevis oocytes showing that RhoE was also modified in vivo by C3Stau but not by C3 from C. botulinum. The poor cell accessibility of C3Stau was overcome by generation of a chimeric toxin recruiting the cell entry machinery of C. botulinum C2 toxin. The chimeric C3Stau caused the same morphological and cytoskeletal changes as the chimeric C. botulinum C3. C3Stauis a new member of the family of the C3-like transferases but is also the prototype of a subfamily of RhoE/Rnd modifying transferases.