We describe and discuss the most recent findings on the activity and function of the oligomeric AAA+ chaperone ClpB from the Hsp100 protein family in pathogenic microorganisms. Pathogens are exposed to significant str...We describe and discuss the most recent findings on the activity and function of the oligomeric AAA+ chaperone ClpB from the Hsp100 protein family in pathogenic microorganisms. Pathogens are exposed to significant stress during infection of the host cells, frequently resulting in protein aggregation. The fact that ClpB is usually up-regulated in pathogens together with its immune reactivity suggests that ClpB acting as a protein disaggregase may be important for pathogen invasion and virulence. However, the specific function of ClpB in pathogenicity is still unclear. Since it is known that ClpB does not exist in mammals, it may serve as a potential target for the development of an effective therapy against several major bacterial diseases that do not respond to conventional antibiotics.展开更多
目的探讨酪蛋白水解肽酶B同源物(caseinolytic peptidase B homolog,CLPB)基因变异所致3-甲基戊烯二酸尿症Ⅶ型的遗传学病因。方法回顾性分析1例在贵州医科大学附属医院诊断为3-甲基戊烯二酸尿症Ⅶ型患儿的分子生物学特征。提取患儿外...目的探讨酪蛋白水解肽酶B同源物(caseinolytic peptidase B homolog,CLPB)基因变异所致3-甲基戊烯二酸尿症Ⅶ型的遗传学病因。方法回顾性分析1例在贵州医科大学附属医院诊断为3-甲基戊烯二酸尿症Ⅶ型患儿的分子生物学特征。提取患儿外周血白细胞DNA,应用高通量测序技术进行基因变异分析,并用Sanger测序进行家系验证。结果患儿生后出现四肢强直、口周发绀,曾因"新生儿低钙血症、新生儿低血糖、新生儿黄疸(ABO溶血)"住院治疗。1岁1月龄因"发热4 d"后出现不能独坐、竖头不稳、进食呛咳,反复呼吸道感染,肌张力增高,尿代谢筛查示3-甲基戊烯二酸浓度为34.98 mmol/molCr。肌电图提示双侧腓总神经运动传导速度均渐慢,双侧腓浅神经感觉传导速度均轻度渐慢,且波幅均降低。脑电图在24 h内监测到18次癫痫临床发作。头颅MRI见脑发育欠佳,额叶及小脑为著;髓鞘化延迟。基因检测结果显示患儿CLPB基因存在c.1016T>G(p.L339R)和c.130delG(p.E44Sfs*5)复合杂合变异;患儿母亲携带CLPB基因c.1016T>G(p.L339R)杂合变异,患儿父亲携带CLPB基因c.130delG(p.E44Sfs*5)杂合变异。患儿的变异分别来自父亲和母亲,均为未报道过的新变异。c.130delG(p.E44Sfs*5)杂合变异按照美国医学遗传学与基因组学学会指南评价为可能致病性。结论分别来自母亲和父亲的CLPB基因c.1016T>G(p.L339R)和c.130delG(p.E44Sfs*5)复合杂合变异可能为该患儿的致病原因。展开更多
文摘We describe and discuss the most recent findings on the activity and function of the oligomeric AAA+ chaperone ClpB from the Hsp100 protein family in pathogenic microorganisms. Pathogens are exposed to significant stress during infection of the host cells, frequently resulting in protein aggregation. The fact that ClpB is usually up-regulated in pathogens together with its immune reactivity suggests that ClpB acting as a protein disaggregase may be important for pathogen invasion and virulence. However, the specific function of ClpB in pathogenicity is still unclear. Since it is known that ClpB does not exist in mammals, it may serve as a potential target for the development of an effective therapy against several major bacterial diseases that do not respond to conventional antibiotics.
