谷氨酰胺脱酰胺作用和泛素/NEDD8 的功能障碍由细菌效应物家族引起。
Glutamine deamidation and dysfunction of ubiquitin/NEDD8 induced by a bacterial effector family.
机构信息
Graduate Program in Chinese Academy of Medical Sciences and Beijing Union Medical College, Beijing 100730, China.
出版信息
Science. 2010 Sep 3;329(5996):1215-8. doi: 10.1126/science.1193844. Epub 2010 Aug 5.
Abstract
A family of bacterial effectors including Cif homolog from Burkholderia pseudomallei (CHBP) and Cif from Enteropathogenic Escherichia coli (EPEC) adopt a functionally important papain-like hydrolytic fold. We show here that CHBP was a potent inhibitor of the eukaryotic ubiquitination pathway. CHBP acted as a deamidase that specifically and efficiently deamidated Gln40 in ubiquitin and ubiquitin-like protein NEDD8 both in vitro and during Burkholderia infection. Deamidated ubiquitin was impaired in supporting ubiquitin-chain synthesis. Cif selectively deamidated NEDD8, which abolished the activity of neddylated Cullin-RING ubiquitin ligases (CRLs). Ubiquitination and ubiquitin-dependent degradation of multiple CRL substrates were impaired by Cif in EPEC-infected cells. Mutations of substrate-contacting residues in Cif abolished or attenuated EPEC-induced cytopathic phenotypes of cell cycle arrest and actin stress fiber formation.
摘要
一个包括伯克霍尔德氏菌假单胞菌（CHBP）和肠致病性大肠杆菌（EPEC）的 Cif 同源物在内的细菌效应物家族采用了一种具有重要功能的木瓜样水解折叠。我们在这里表明，CHBP 是真核生物泛素化途径的有效抑制剂。CHBP 作为脱酰胺酶，可特异性且有效地在体外和伯克霍尔德菌感染期间使泛素和类泛素蛋白 NEDD8 中的 Gln40 脱酰胺。脱酰胺的泛素在支持泛素链合成方面受到损害。Cif 特异性脱酰胺化 NEDD8，从而使 neddylated Cullin-RING 泛素连接酶（CRL）失活。EPEC 感染细胞中的 Cif 会损害多种 CRL 底物的泛素化和泛素依赖性降解。Cif 中底物接触残基的突变会消除或减弱 EPEC 诱导的细胞周期停滞和肌动蛋白应激纤维形成的细胞病变表型。
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Cullin mediates degradation of RhoA through evolutionarily conserved BTB adaptors to control actin cytoskeleton structure and cell movement.Cullin通过进化上保守的BTB衔接蛋白介导RhoA的降解，以控制肌动蛋白细胞骨架结构和细胞运动。
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