Crystal structure of Middle East respiratory syndrome coronavirus helicase

Autor: Wei Hao, Rajat S. Das, Sheng Cui, Meitian Wang, Ruiyun Han, Justyna Aleksandra Wojdyla, Rong Zhao, Muthiah Manoharan, Ivan Zlatev
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
RNA viruses
Adenosine Triphosphatase
Models
Molecular
Coronaviruses
viruses
medicine.disease_cause
Pathology and Laboratory Medicine
Biochemistry
Protein Structure
Secondary
Database and Informatics Methods
Protein structure
Medicine and Health Sciences
lcsh:QH301-705.5
Coronavirus
Genetics
Crystallography
Physics
virus diseases
Condensed Matter Physics
RNA Helicase A
Enzymes
Chemistry
Zinc
Medical Microbiology
Viral Pathogens
Viruses
Physical Sciences
Crystal Structure
Middle East Respiratory Syndrome Coronavirus
Helicases
Pathogens
Coronavirus Infections
Sequence Analysis
Research Article
Chemical Elements
lcsh:Immunologic diseases. Allergy
Multiple Alignment Calculation
Middle East respiratory syndrome coronavirus
Bioinformatics
Immunology
Sequence alignment
Biology
Research and Analysis Methods
Microbiology
03 medical and health sciences
Sequence Motif Analysis
Virology
Computational Techniques
medicine
Solid State Physics
Humans
Protein Interaction Domains and Motifs
Nucleic acid structure
Molecular Biology
Microbial Pathogens
Biology and life sciences
Organisms
Phosphatases
DNA Helicases
Helicase
Proteins
Split-Decomposition Method
respiratory tract diseases
030104 developmental biology
lcsh:Biology (General)
biology.protein
Enzymology
Parasitology
lcsh:RC581-607
Sequence Alignment
Zdroj: PLoS Pathogens
PLOS Pathogens
PLoS Pathogens, Vol 13, Iss 6, p e1006474 (2017)
ISSN: 1553-7374
1553-7366
Popis: 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.
Author summary Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) caused global pandemics in 2003 and 2012 with the fatality rates of 10–35%. Outbreak of MERS-CoV in the Republic of Korea in 2015 highlighted that the newly emerged CoVs remain a concern for the public health. Nevertheless, effective vaccine and drug against CoVs are still missing. Among CoV-encoded nonstructural proteins (nsps), nsp13 helicase is considered one of the most important drug targets. Nsp13 is a highly conserved protein in CoVs and nidovirales and one of the two central components of the membrane associated replication-transcription complex, which performs viral RNA synthesis. However, despite decades of structural characterization of CoV-encoded proteins, the structure of nsp13 remained unavailable. In this study, we determined the first crystal structure of the full-length MERS-CoV nsp13. MERS-CoV helicase has an N-terminal Cys/His rich domain (CH) with three zincs, a beta-barrel domain and a C-terminal SF1 helicase core. While the domain organization of nsp13 is similar to arterivirus nsp10, the individual domains of nsp13 are closely related to their equivalent domains of eukaryotic Upf1 helicases. Our findings provide novel structural information essential for structure-based drug design against CoV.
Databáze: OpenAIRE
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