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Cell's gatekeeper for ammonia revealed in unprecedented detail

Bacteria thrive on it, red blood cells carry it in high concentration, yet the human brain can't tolerate it. The ability of cells to acquire or dispose of ammonia can be a matter of life and death. In the September 10 issue of Science, UCSF researchers publish the first atomic-level structure of the channel that controls the passage of ammonia in and out of cells.

The complex structure -- depicted on the cover of Science -- was determined in greater detail than that of any cell membrane channel yet described. The structure can help reveal the molecular basis of often life-threatening diseases caused by ammonia toxicity, and provides the "template for designing drugs to treat the diseases," said Robert Stroud, PhD, professor of biochemistry and biophysics and of pharmaceutical chemistry at UCSF and senior author of the paper in Science.

Knowledge of the channel architecture is also expected to help explain how ammonia, carbon dioxide and other gases are taken in, transported between cells and excreted, the scientists said.

The issue of Science also includes a "Perspective" article about the significance of determining the structure and its likely mode of action.

The three-dimensional shape of other cell membrane channels -- those that conduct water and charged molecules called ions -- have been reported over the past six years. In 2000, Stroud's group was the first to discover the structure and mechanisms of the water-conducting channels.

To determine the structure of an ammonia channel, the UCSF scientists focused on AmtB, a protein that facilitates ammonia uptake in bacteria. The bacterial AmtB is a member of a "superfamily" of protein channels with very similar amino acid sequences and very similar functions in all species. Humans have four members of this superfamily of cell membrane channels. They are the Rh factors, most familiar as the Rh blood group antigens on the surface of red blood cells that can caus
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
9-Sep-2004


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