Hao Wei, Wojdyla Justyna Aleksandra, Zhao Rong, Han Ruiyun, Das Rajat, Zlatev Ivan, Manoharan Muthiah, Wang Meitian, Cui Sheng
MOH key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, No.9 Dong Dan San Tiao, Beijing, China.
Swiss Light Source at Paul Scherrer Institute, Villigen, Switzerland.
PLoS Pathog. 2017 Jun 26;13(6):e1006474. doi: 10.1371/journal.ppat.1006474. eCollection 2017 Jun.
Middle East respiratory syndrome coronavirus (MERS-CoV) remains a threat to public health worldwide; however, effective vaccine or drug against CoVs remains unavailable. CoV helicase is one of the three evolutionary most conserved proteins in nidoviruses, thus making it an important target for drug development. We report here the first structure of full-length coronavirus helicase, MERS-CoV nsp13. MERS-CoV helicase has multiple domains, including an N-terminal Cys/His rich domain (CH) with three zinc atoms, a beta-barrel domain and a C-terminal SF1 helicase core with two RecA-like subdomains. Our structural analyses show that while the domain organization of nsp13 is conserved throughout nidoviruses, the individual domains of nsp13 are closely related to the equivalent eukaryotic domains of Upf1 helicases. The most distinctive feature differentiating CoV helicases from eukaryotic Upf1 helicases is the interaction between CH domain and helicase core.
中东呼吸综合征冠状病毒（MERS-CoV）仍然是全球公共卫生的一大威胁；然而，针对冠状病毒的有效疫苗或药物仍然无法获得。冠状病毒解旋酶是巢病毒中进化上最保守的三种蛋白质之一，因此使其成为药物开发的重要靶点。我们在此报告全长冠状病毒解旋酶MERS-CoV nsp13的首个结构。MERS-CoV解旋酶有多个结构域，包括一个含有三个锌原子的N端富含半胱氨酸/组氨酸的结构域（CH）、一个β桶状结构域和一个带有两个类RecA亚结构域的C端SF1解旋酶核心。我们的结构分析表明，虽然nsp13的结构域组织在整个巢病毒中是保守的，但nsp13的各个结构域与Upf1解旋酶的等效真核结构域密切相关。冠状病毒解旋酶与真核Upf1解旋酶最显著的区别特征是CH结构域与解旋酶核心之间的相互作用。
