title: Structural basis for the regulatory function of a complex zinc-binding domain in a replicative arterivirus helicase resembling a nonsense-mediated mRNA decay helicase.
abstract: All positive-stranded RNA viruses with genomes>∼7 kb encode helicases, which generally are poorly characterized. The core of the nidovirus superfamily 1 helicase (HEL1) is associated with a unique N-terminal zinc-binding domain (ZBD) that was previously implicated in helicase regulation, genome replication and subgenomic mRNA synthesis. The high-resolution structure of the arterivirus helicase (nsp10), alone and in complex with a polynucleotide substrate, now provides first insights into the structural basis for nidovirus helicase function. A previously uncharacterized domain 1B connects HEL1 domains 1A and 2A to a long linker of ZBD, which further consists of a novel RING-like module and treble-clef zinc finger, together coordinating three Zn atoms. On substrate binding, major conformational changes were evident outside the HEL1 domains, notably in domain 1B. Structural characterization, mutagenesis and biochemistry revealed that helicase activity depends on the extensive relay of interactions between the ZBD and HEL1 domains. The arterivirus helicase structurally resembles the cellular Upf1 helicase, suggesting that nidoviruses may also use their helicases for post-transcriptional quality control of their large RNA genomes.
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China, Department of Medical Microbiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands, Clinical Medicine Research Center, Affiliated Hospital of Guangdong Medical College, Guangdong 524001, China, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China, Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China and Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119991, Russia.
authors.forename: Zengqin
authors.initials: Z
authors.lastname: Deng
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Lehmann
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Li
authors.forename: Chong
authors.initials: C
authors.lastname: Feng
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Qi
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.forename: Xingliang
authors.initials: X
authors.lastname: Zhang
authors.forename: Wenhai
authors.initials: W
authors.lastname: Feng
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Peng
authors.initials: P
authors.lastname: Gong
authors.forename: Ye
authors.initials: Y
authors.lastname: Tao
authors.forename: Clara C
authors.initials: CC
authors.lastname: Posthuma
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Snijder
authors.forename: Alexander E
authors.initials: AE
authors.lastname: Gorbalenya
authors.forename: Zhongzhou
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D007240:Equartevirus / Q000201:enzymology*; D008958:Models, Molecular; D059365:Nonsense Mediated mRNA Decay; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000737:chemistry
chemical_list: D014764:Viral Proteins; D004247:DNA; D000251:Adenosine Triphosphatases; D020365:RNA Helicases; D015032:Zinc