Crystal Structure Of Key HIV Protein Reveals New Treatment Targets

In a finding that unlocks new doors to devising drugs and vaccines against HIV, scientists have crystallized the core of gp120, the surface protein molecule that the virus uses to attach itself to immune system cells.

The new model of the gp120 core's crystal structure reveals specific targets for anti-HIV vaccines and drugs, and highlights the surprising array of defenses that the virus uses to evade attack.

"Studying the gp120 crystal's structure can tell us a lot more about how the virus locks on to immune system cells," says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID). "We now have specific target sites on which to focus in developing new drugs and vaccines."

The research, funded in part by NIAID, comes from a team led by Joseph G. Sodroski, M.D., of the Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass., and Wayne Hendrickson, Ph.D., of Columbia University College of Physicians and Surgeons, New York, N.Y. Their work appears in the June 18, 1998, issue of Nature and the June 19, 1998, issue of Science.

The scientists confirmed several previously known features but also found some surprises in the crystal structure of the protein. "We discovered that a large part of the gp120 surface is protected against attack by a dense array of carbohydrates and by an amazing capacity to change shape," says Dr. Sodroski.

Among their findings were:

  1. A shape-shifting device that allows gp120 to shield itself from antibodies until it reaches CD4 receptor sites on the immune system's T-cells - the first step in hijacking these cells. Loop-shaped projections that stick out above the molecule's surface hide the critical locking regions. When the virus reaches its target, the loops collapse and move out of the way, unmasking the locking regions.

  2. An icing of carbohydrate molecules that also shields the receptor-binding regions of the gp120 surface from a

Contact: June Wyman
NIH/National Institute of Allergy and Infectious Diseases

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