The Dengue Virus Envelope Protein is a glycoprotein that shows how huge conformational shifts can be brought about by environmental changes in pH which lead to amazing functional significance. The glycoprotein forms a capsule around the lipid membrane of the virus with 180 copies of the protein that are anchored to the lipid membrane of the virus (1).
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GLYCOPROTEIN CAPSULE http://www.virology.wisc.edu/virusworld/PS10/dng_dengue_virus_vmd.jpg |
When forming a capsid the protein is associated as dimers. Once the virus capsid is taken up into a target cell via endocytosis things begin to get interesting. Endosomes utilize pH pumps to maintain a lower pH than the cytosol. This drop in pH inside the endosome causes the protein to undergo a large conformational shift (39 angstroms) (2) breaking the association of the dimers and leading to the formation of trimers. These trimers form spikes on the surface of the virus lipid membrane that have hydrophobic tips. These tips also known as fusion loops can insert into the target membrane of the endosome. The protein then undergoes a further conformatinal change in which the N and C termini are drawn together. This serves to make the protein fold in on itself and rotates the entire trimer 90 degrees in relation to the membranes. This draws the two membranes together allowing them to fuse and create a lipidic fusion pore through which the virus can dump its RNA into the cytosol of the target cell.
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MEMBRANE FUSION PROCESS
Modis, Yorgo, Steven Ogata, David Clements, and Stephen Harrison. "Structure of the dengue virus envelope protein after membrane fusion." Nature 427 (2004): 313-19
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DENGUE VIRUS ANIMATION
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| Single Protein Image made in PyMol from PDB File 1OK8 |
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| Protein Dimer in Membrane State Image made in Pymol from PDB File 3J27 |
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| Protein Trimer Ready for Fusion http://www.rcsb.org/pdb/101/motm.do?momID=103 |
Resources
1. http://www.rcsb.org/pdb/101/motm.do?momID=103 (PDM Molecule of the Month)
I really enjoyed the figures of this protein as well as the short video clip. For me, there was a little confusion to how the first paragraph and second paragraphs fit together. The only reason I think this is because at the beginning it says your protein is a glycoprotein and then at the end it says the glycoprotein surrounds the virus which has the e protein. besides that it is a great post.
ReplyDeleteI liked that you made use of a video! I also think that your explanation is concise and informative. However, I would like to have read about more detail such as how the pH change occurs and how the pH specifically affects the protein.
ReplyDeleteI think your protein is really cool! If possible I would have liked to see a picture of just one of the glycoproteins to get an idea of what it looks like. I also was wondering if you could explain more in detail what the pH change does to cause the conformational change. I really liked the video, and the page overall. Nicely done!
ReplyDeletePlease show us some of the structures you've made, too!
ReplyDelete