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Crystal Structure Of gp120 Reveals HIV In Action

NEW YORK, NY, 1998 -- In the long battle against AIDS, a philosophy of "know the enemy" has guided basic research. Specifically, investigators have sought a viral Achilles heel by dissecting the precise molecular choreography that unfolds as HIV penetrates the linchpin-like T cells of the immune system. Now, an unprecedented peek at that process -- a viral surface glycoprotein caught in the act of binding a CD4 T cell receptor -- graces the covers of both the June 18 issue of Nature and the June 19 issue of Science magazines.

The long-sought crystal structure of gp120 in action is a collaborative effort led by researchers from the Columbia University College of Physicians & Surgeons, and the Dana-Farber Cancer Institute. "The crystal structure tells us how the virus is able to bind to the receptor at the same time that it remains sufficiently changeable to avoid immune detection. There is the potential for the information to be used to design compounds that interfere and block that interaction," says Wayne Hendrickson, Ph.D., professor of biochemistry and molecular biophysics at Columbia University and a Howard Hughes Medical Institute Investigator. Adds Peter Kwong, Ph.D., associate research scientist at Columbia and lead author on the first Nature paper, "Knowing the structure down to the atomic details will provide valuable clues for vaccine design."

X-ray crystallography is a technique that passes X-rays through a crystal from many angles, determines their pattern of diffraction, and then assembles the data to reveal the crystal's 3-dimensional structure, or conformation. The technique was key in solving the structure of DNA in 1953 and, more recently, in discovering the structure of HIV protease, which led to development of protease inhibitors.

But X-ray crystallography requires crystallizing a compound, which was no small feat for gp120. "The mechanisms that HIV has to protect itself from
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Contact: Carolyn Conway
cc328@columbia.edu
212-305-3900
Columbia University Medical Center
17-Jun-1998


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