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MONA SINGH |
Sequence-based methods for coiled coil recognition, with applications to studying viral membrane fusion proteins |
Progress: Previously, we devised an iterative algorithm that uses randomness
and statistical techniques to improve existing methods for recognizing
protein structural motifs. Our algorithm was tested on the domain of three-stranded
coiled coils and subclasses of two-stranded coiled coils. During the initial
development of our iterative method, we identified two coiled coil-like
regions in the HIV membrane fusion protein that no previous program identified.
In fact, in the Kim Lab, crystallographic studies of HIV have demonstrated
that these two coiled coil-like motifs interact with each other to form
what may be a new motif that plays a critical role in membrane fusion. |
Using our iterative method, we have newly identified coiled coil-like
regions in many retrovirus, paramyxovirus and filovirus membrane fusion
proteins. Additionally, sequence analyses of these proteins outside their
putative coiled-coil domains illustrate some structural differences between
them. Complementing previous crystallographic studies, our findings provide
further evidence that the 3-stranded coiled coil is a common motif found
in many diverse viral membrane-fusion proteins. The abundance and structural
conservation of this motif, even in the absence of sequence homology, suggests
that it is critical for viral-cellular membrane fusion. Several of our
predictions have very recently been experimentally verified, including
those for Ebola virus, visna virus and human T-cell leukemia virus. |
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