Hyatt, JG, Prévost, S, Devos, JM, Mycroft-West, CJ, Skidmore, MA ORCID: https://orcid.org/0000-0002-0287-5594 and Winter, A ORCID: https://orcid.org/0000-0002-8602-8009 (2020) Molecular Changes in Dengue Envelope Protein Domain III upon Interaction with Glycosaminoglycans. Pathogens, 9 (11).

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Abstract

Dengue fever is a rapidly emerging vector-borne viral disease with a growing global burden of approximately 390 million new infections per annum. The Dengue virus (DENV) is a flavivirus spread by female mosquitos of the aedes genus, but the mechanism of viral endocytosis is poorly understood at a molecular level, preventing the development of effective transmission blocking vaccines (TBVs). Recently, glycosaminoglycans (GAGs) have been identified as playing a role during initial viral attachment through interaction with the third domain of the viral envelope protein (EDIII). Here, we report a systematic study investigating the effect of a range of biologically relevant GAGs on the structure and oligomeric state of recombinantly generated EDIII. We provide novel in situ biophysical evidence that heparin and chondroitin sulphate C induce conformational changes in EDIII at the secondary structure level. Furthermore, we report the ability of chondroitin sulphate C to bind EDIII and induce higher-order dynamic molecular changes at the tertiary and quaternary structure levels which are dependent on pH, GAG species, and the GAG sulphation state. Lastly, we conducted ab initio modelling of Small Angle Neutron Scattering (SANS) data to visualise the induced oligomeric state of EDIII caused by interaction with chondroitin sulphate C, which may aid in TBV development.

Item Type: Article
Additional Information: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Uncontrolled Keywords: dengue virus; envelope protein; glycosaminoglycans; protein-glycosaminoglycan interactions; small-angle scattering
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history
Divisions: Faculty of Natural Sciences > School of Life Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 08 Dec 2020 13:09
Last Modified: 22 Dec 2020 11:11
URI: https://eprints.keele.ac.uk/id/eprint/8997

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