The dengue virus envelope protein exists in two
conformations. The conformational shift is stimulated by a change in pH. At pH
>7 it exists as a dimer. When pH<7 the three domains of the protein shift
, moving the C terminus a full 39 angstroms and causing the protein to
associate into trimers. These conformational changes take it from providing a
flat membrane surface in its high pH conformation to creating trimer “spikes”
in its second conformation. These spikes are used to puncture endosomes and
allow entrance of the virus into the cell.
Modis, Yorgo, Steven Ogata, David
Clements, and Stephen Harrison. "Structure of the dengue virus envelope
protein after membrane fusion" Nature 427 (2004): 313-19
The dengue virus is a flavivirus which is an insect-borne
virus. Flaviviruses fuse to membranes via E proteins which are the primary
external protein of the virion. The dengue virus envelope protein associates
into a trimer in low pH environments. This trimer has a hydrophobic tip the inserts
itself into the outer leaflet of the target membrane bilayer. The protein then undergoes
more rearrangements that bring the membrane of the virus and the membrane of
the target cell together to allow fusion of the membranes and release of the
virus into the cytosol.
Schmidt, Aaron G., Priscilla L.
Yang, and Stephen C. Harrison. "Peptide inhibitors of dengue-virus entry
target a late-stage fusion intermediate" PLoS Pathogens 6.4
(2010): 1-11.
The conformational change of the dengue virus envelope
protein is initiated by cleavage of the dimer associations. This occurs at low
pH (5.0-6.0). the conformational change is reversible. The fusion of the
protein with the target membrane occurs once prM (a peptide blocking the
hydrophobic tip used for initial membrane fusion/anchoring) is cleaved from the
trimers.
Yu, I-mei, Wei Zhang, Heather
Holdaway, Long Li, and Victor Kostyuchenko. "Structure of the immature
dengue virus at low pH primes proteolytic maturation" Science 319
(2008): 1834-37.
