Department of Biochemistry, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada.
Department of Biochemistry, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada.
Structure. 2014 Feb 4;22(2):250-9. doi: 10.1016/j.str.2013.11.006. Epub 2013 Dec 26.
Upon host cell infection, pathogenic Escherichia coli hijacks host cellular processes with the help of 20-60 secreted effector proteins that subvert cellular processes to create an environment conducive to bacterial survival. The NleH effector kinases manipulate the NF-κB pathway and prevent apoptosis. They show low sequence similarity to human regulatory kinases and contain two domains, the N-terminal, likely intrinsically unfolded, and a C-terminal kinase-like domain. We show that these effectors autophosphorylate on sites located predominantly in the N-terminal segment. The kinase domain displays a minimal kinase fold, but lacks an activation loop and the GHI subdomain. Nevertheless, all catalytically important residues are conserved. ATP binding proceeds with minimal structural rearrangements. The NleH structure is the first for the bacterial effector kinases family. NleHs and their homologous effector kinases form a new kinase family within the cluster of eukaryotic-like kinases that includes also Rio, Bud32, and KdoK families.
当宿主细胞受到感染时，致病性大肠杆菌在 20-60 种分泌效应蛋白的帮助下劫持宿主细胞的过程，这些蛋白颠覆了细胞过程，创造了有利于细菌生存的环境。NleH 效应激酶操纵 NF-κB 途径并阻止细胞凋亡。它们与人类调节激酶的序列相似性低，包含两个结构域，即 N 端可能固有地无规卷曲的结构域和 C 端激酶样结构域。我们表明这些效应物主要在 N 端片段上发生自身磷酸化。激酶结构域显示出最小的激酶折叠，但缺乏激活环和 GHI 亚结构域。尽管如此，所有催化重要的残基都被保守。ATP 结合伴随着最小的结构重排。NleH 结构是细菌效应激酶家族的第一个结构。NleHs 和它们的同源效应激酶在包括 Rio、Bud32 和 KdoK 家族在内的真核样激酶簇中形成了一个新的激酶家族。
