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Structural study of the C-terminal domain of non-structural protein 1 from Japanese encephalitis virus

DOI: 10.1128/JVI.01868-17 DOI Help

Authors: Thanalai Poonsiri (University of Liverpool) , Gareth S. A. Wright (University of Liverpool) , Michael S. Diamond (Washington University in St. Louis) , Lance Turtle (University of Liverpool) , Tom Solomon (University of Liverpool) , Svetlana V. Antonyuk (University of Liverpool)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Virology

State: Published (Approved)
Published: January 2018
Diamond Proposal Number(s): 11740

Abstract: Japanese encephalitis virus (JEV) is a mosquito-transmitted Flavivirus that is closely related to other emerging viral pathogens including dengue, West Nile (WNV) and Zika viruses. JEV infection can result in meningitis and encephalitis, which in severe cases cause permanent brain damage and death. JEV occurs predominantly in rural areas throughout Southeast Asia, the Pacific islands and the Far East, causing around 68,000 cases worldwide each year. In this study, we present a 2.1 Å resolution crystal structure of the C-terminal β-ladder domain of JEV non-structural protein 1 (NS1-C). The surface charge distribution of JEV NS1-C is similar to WNV and ZIKV but differs form DENV. Analysis of the JEV NS1-C structure, with in silico molecular dynamics simulation and experimental solution small angle X-ray scattering, indicates extensive loop flexibility on the exterior of the protein. This, together with the surface charge distribution, indicates flexibility influences the protein-protein interactions that govern pathogenicity. These factors also affect the interaction of NS1 with the monoclonal antibody, 22NS1, which is protective against West Nile virus infection. Liposome and heparin binding assays indicate that only the N-terminal region of NS1 mediates interaction with membranes, and that sulfate binding sites common to NS1 structures are not glycosaminoglycan binding interfaces. This study highlights several differences between flavivirus NS1 proteins and contributes to our understanding of their structure-pathogenic function relationships.

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography

Other Facilities: SOLEIL