Biophysical characterization and vector-specific antagonist activity of domain III of the tick-borne flavivirus envelope protein.
The molecular determinants responsible for flavivirus host cell binding and tissue tropism are largely unknown, although domain III of the envelope protein has been implicated in these functions. We examined the solution properties and antagonist activity of Langat virus domain III. Our results suggest that domain III adopts a stably folded structure that can mediate binding of tick-borne flaviviruses but not mosquito-borne flaviviruses to their target cells. Three clusters of phylogenetically conserved residues are identified that may be responsible for the vector-specific antagonist activity of domain III.
Department of Human Biological Chemistry & Genetics and Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
S
S
Bhardwaj
M
M
Holbrook
R E
RE
Shope
A D
AD
Barrett
S J
SJ
Watowich
D000595:Amino Acid Sequence; D000818:Animals; D002522:Chlorocebus aethiops; D002942:Circular Dichroism; D017124:Conserved Sequence; D004669:Encephalitis Viruses, Tick-Borne / Q000187:drug effects* / Q000378:metabolism; D005416:Flavivirus / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D013379:Substrate Specificity; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
D010446:Peptide Fragments; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C065696:glycoprotein E, Flavivirus