Toxic proteins in black widow spider venom and some sea anemone toxins share the same strategy--they punch huge holes in the cell membranes of their victims. Pharmaceutical companies harness this strategy in the potent antifungal medications amphotericin and nystatin. Yet until recently, researchers have known little about how such membrane-piercing proteins work.
Now, using an innovative technique, NIH-funded researchers at New York City's Albert Einstein College of Medicine are closing in on how one such protein operates. Their work may shed light not only on the deadly power of certain toxins, but on diseases like cystic fibrosis that result from defects in natural membrane channels.
"If we could understand how this protein works, we might understand more about how proteins are normally moved across and inserted into membranes," said the study's lead scientist, Dr. Alan Finkelstein, a professor in the Department of Physiology and Biophysics and the Department of Neuroscience. "Why do we care about that? Because it is relevant to all the proteins that end up inserted in the cell's membrane [such as hormone receptors] as well as to any kind of excreted protein [like digestive enzymes]."
In a paper published in the March 1996 issue of the
Journal of General Physiology, the researchers mapped
out a rough structure of two conformations of colicin Ia, a
toxin produced by some strains of E. coli bacteria to kill
competing bacteria. From their previous work, the scientists
knew that a portion of colicin Ia changes from a harmless
cluster of about 175 amino acids into a lethal structure
that harpoons the inner membrane of its bacterial victim.
The resulting hole, or
Contact: Alisa Zapp
NIH/National Institute of General Medical Sciences