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in The Biology Files
GP120 UNDRESSED...
Kudos to Harvard/Howard Hughes Institute ('The Aviator' guy!) and Scripps Research Institute researchers for solving the structures of two key proteins that HIV uses to hijack cell machinery. One of these, gp120, is a surface viral protein and is particularly diabolical, and crucial for the virus to bind and recognise helper T cells. These studies mark a major advance in the understanding of the disease and would hopefully point the way toward a vaccine/cure.
Tragically, one of the lead authors on the Harvard paper is Don Wiley, a biochemist who was found dead in 2001 under sudden and suspicious circumstances. That's a long story in its own right, and you can read about it here. Among other things, suspicions that his death was a murder were based on the fact that he worked with insidious viruses which could have bioterrorism prospects. Wiley was a student of William Lipscomb, Nobel Laureate, who in turn was a student of the legendary Linus Pauling. Lipscomb got the Nobel for studies of boranes, but later switched to impressive structural studies of proteins.
This important paper would be a fitting tribute to Wiley's memory.
Here are a few excerpts from the news article:
"Dennis Burton and Ian Wilson, immunologists at The Scripps Research Institute in La Jolla, California, have looked at 4E10, the most broadly acting HIV antibody known so far. They have worked out the structure that it has when it is bound to gp41, the protein (or antigen) that it recognizes on the virus's surface, and they have published their results in Immunity. The pair hope to use the information to design a vaccine that will stimulate the production of antibodies like 4E10. "We can make a mimic of the antigen that will elicit the same type of antibodies we initially studied," says Wilson. He and Burton call the approach retrovaccinology."
"The structure of the second protein is published in this week's Nature by researchers led by the structural biologist Stephen Harrison of Harvard Medical School, Boston. They reveal the crystal structure of the virus surface protein gp120 from the simian immunodeficiency virus, which is closely related to HIV.The researchers studied the structure of the protein as it is before it binds to a helper T cell, a type of immune cell that HIV infects. The bound structure was solved several years ago, so the new information helps to show how the molecule changes shape when it recognizes and binds to the cell."
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For anyone interested in this work, i also suggest some research done using micelles with the CD4 receptor implanted to "trick" the HIV virus into binding it...this is probably a crappy post b/c i cannot remember the authors or PI of the work. =(
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