Using x-ray crystallography, a team of scientists led by Howard Hughes Medical Institute investigator Roderick MacKinnon at The Rockefeller University has determined the three-dimensional structure of the chloride ion channel. The images, which were reported in the January 17, 2002, issue of the journal Nature, reveal an entirely new type of protein architecture designed to be an efficient conductor of chloride anions across the membrane of cells.
The results, called a spectacular breakthrough by Thomas Jentsch of the Center for Molecular Neurobiology in Hamburg, Germany, in an accompanying News and Views article, resolve a confusing series of biochemical studies that failed to explain how the channel works.
It is a complicated structure, said MacKinnon. Scientists did an excellent job deducing many aspects of the chloride ion channel, for example, its dimer architecture was predicted 20 years ago by HHMI investigator Christopher Miller at Brandeis University, and firmly established more recently by his laboratory using biochemical methods and electron microscopy. But to understand the physical principles of anion selectivity, an atomic structure is needed. Although the structure is complicated, it conveys a simple message of how nature arranged the protein to stabilize an anion such as chloride inside the membrane.
Electrically charged ions are used by living organisms for many types of signaling, including controlling the heart rhythm, generating nerve impulses and secreting hormones. Cells use ions to signal by creating an electrical charge difference between
Contact: Jim Keeley
Howard Hughes Medical Institute