Solution structure and structural dynamics of envelope protein domain III of mosquito- and tick-borne flaviviruses

Shaoning Yu, Alice Wuu, Reneeta Basu, Michael R. Holbrook, Alan D.T. Barrett, J. Ching Lee

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The mosquito-borne West Nile (WNV) and dengue 2 (DEN2V) viruses and tick-borne Langat (LGTV) and Omsk hemorrhagic fever (OHFV) viruses are arthropod-borne flaviviruses (family Flaviviridae, genus Flavivirus). These viruses are quite similar at both the nucleotide and amino acid level, yet they are very divergent in their biological properties and in the diseases they cause. The objective of this study was to examine the putative receptor-binding domains of the flaviviruses, the envelope (E) protein domain III (D3), which assume very similar structures either as part of the whole envelope protein or as individual entities, and to define the biophysical properties that distinguish among these viruses. Circular dichroism and Fourier transform infrared spectroscopy were employed to monitor the solution structure of these proteins. While the spectroscopic results found that the D3 from each of these viruses is composed of either β-sheets or β-turns, which is consistent with X-ray crystal data for tick-borne encephalitis and dengue viruses, these results reveal that recombinant D3s (rED3s) derived from tick-borne flaviviruses (LGT-rED3 and OHF-rED3) were similar to each other, while those from mosquito-borne flaviviruses (WN-rED3 and DEN-rED3) were similar to each other yet distinct from-rED3 of the tick-borne viruses. Protein dynamic studies probed by fluorescence quenching and hydrogen/deuterium exchange found that the rED3s are dynamic entities. The tick-borne proteins again exhibit very similar dynamic properties, which are different from the mosquito-borne proteins. The WN-rED3 is significantly less stable than the other three rED3s. Overall, these differences in biophysical properties correlate with biological properties of these viruses that tick-borne flaviviruses are more stable than mosquito-borne flaviviruses.

Original languageEnglish (US)
Pages (from-to)9168-9176
Number of pages9
JournalBiochemistry
Volume43
Issue number28
DOIs
StatePublished - Jul 20 2004

ASJC Scopus subject areas

  • Biochemistry

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