Institute of Biotechnology, Life Sciences Center, Vilnius University, Sauletekio al. 7, LT-10257 Vilnius, Lithuania.
DNA-Protein Interactions Unit, School of Biochemistry, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
Nucleic Acids Res. 2018 Mar 16;46(5):2560-2572. doi: 10.1093/nar/gky107.
CglI is a restriction endonuclease from Corynebacterium glutamicum that forms a complex between: two R-subunits that have site specific-recognition and nuclease domains; and two H-subunits, with Superfamily 2 helicase-like DEAD domains, and uncharacterized Z1 and C-terminal domains. ATP hydrolysis by the H-subunits catalyses dsDNA translocation that is necessary for long-range movement along DNA that activates nuclease activity. Here, we provide biochemical and molecular modelling evidence that shows that Z1 has a fold distantly-related to RecA, and that the DEAD-Z1 domains together form an ATP binding interface and are the prototype of a previously undescribed monomeric helicase-like motor. The DEAD-Z1 motor has unusual Walker A and Motif VI sequences those nonetheless have their expected functions. Additionally, it contains DEAD-Z1-specific features: an H/H motif and a loop (aa 163-aa 172), that both play a role in the coupling of ATP hydrolysis to DNA cleavage. We also solved the crystal structure of the C-terminal domain which has a unique fold, and demonstrate that the Z1-C domains are the principal DNA binding interface of the H-subunit. Finally, we use small angle X-ray scattering to provide a model for how the H-subunit domains are arranged in a dimeric complex.
CglI 是一种来自谷氨酸棒杆菌的限制内切酶,它形成了一个复合物,其中包括:两个具有特定识别和核酸酶结构域的 R 亚基;以及两个具有 Superfamily 2 解旋酶样 DEAD 结构域和未表征的 Z1 和 C 末端结构域的 H 亚基。H 亚基的 ATP 水解催化双链 DNA 易位,这对于沿着 DNA 的长距离运动激活核酸酶活性是必要的。在这里,我们提供了生化和分子建模证据,表明 Z1 具有与 RecA 远相关的折叠,并且 DEAD-Z1 结构域一起形成了一个 ATP 结合界面,是以前未描述的单体解旋酶样马达的原型。DEAD-Z1 马达具有不寻常的 Walker A 和 Motif VI 序列,但它们具有预期的功能。此外,它还包含 DEAD-Z1 特异性特征:一个 H/H 基序和一个环(aa163-aa172),它们都在 ATP 水解与 DNA 切割的偶联中发挥作用。我们还解析了 C 末端结构域的晶体结构,该结构域具有独特的折叠,并证明 Z1-C 结构域是 H 亚基的主要 DNA 结合界面。最后,我们使用小角度 X 射线散射提供了一个模型,说明 H 亚基结构域在二聚体复合物中的排列方式。