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October 13, 2003
Volume 81, Number 41
CENEAR 81 41 p. 11
ISSN 0009-2347


NOBEL PRIZE

CHEMISTRY PRIZE FOR CELL CHANNELS
Two honored for deciphering how water and ions move in and out of cells

AMANDA YARNELL

This year’s Nobel Prize in Chemistry honors two American physicians-turned-bench-scientists for their work illuminating how ions and water molecules move in and out of cells.

MacKinnon
Courtesy Rockefeller University
Biophysicist and self-taught X-ray crystallographer Roderick MacKinnon of Rockefeller University will split the $1.3 million prize with Peter C. Agre, a professor of biological chemistry at Johns Hopkins University School of Medicine. Although trained as physicians, both Agre, 54, and MacKinnon, 47, have chemical roots. Agre earned a B.A. in chemistry from Augsburg College, in Minnesota, and MacKinnon received his B.A. in biochemistry at Brandeis University.

The membrane-spanning proteins or “channels” that traffic water molecules and ions across cellular membranes control many physiological processes, including nerve function, muscle contraction, and urine production. Malfunctioning channels can cause neurological and cardiac diseases as well as cataracts and other disorders.

“The work has given us an unprecedented insight into how cells function and communicate and will pave the way for researchers to better understand many diseases and develop new and improved medicines,” notes ACS President Elsa Reichmanis.
A Howard Hughes Medical Institute investigator, MacKinnon studies ion channels—membrane-spanning proteins that form a tunnel that allows specific inorganic ions to travel across cell membranes. Such ion channels generate the electrical signals that underlie brain function and the beating of your heart.

For years, ion channel researchers painstakingly mutated individual amino acid residues to determine which ones were important for the proteins’ function. While others dismissed the idea of crystallizing an ion channel as too difficult—and perhaps impossible—MacKinnon jumped in headfirst, teaching himself X-ray crystallography. Just a few years later, in 1998, MacKinnon rocked the field with the first three-dimensional picture of an ion channel.

“MacKinnon’s work has wrought such a breakthrough in the field of ion channels that his Nobel Prize was inevitable,” says Christopher Miller, a biochemistry professor at Brandeis. “I’m thrilled with the prize.”

Since this landmark potassium channel structure, MacKinnon has figured out how this channel allows potassium ions—but not smaller sodium ions—through the membrane. He’s also solved structures of other potassium ion channels, as well as sodium and chloride ion channels. More recently, MacKinnon has shown how chemical and electrical stimuli can force ion channels to open and close.

Scientists predicted the existence of channels for transporting water across membranes more than a century ago. But it wasn’t until 1991 that Agre stumbled upon a small membrane-spanning protein in red blood cells that turned out to be the first member of a large class of water channels that he dubbed aquaporins. Since then, he and others have shown that aquaporin proteins control water transport in most plants and nearly a dozen human tissues.

The aquaporin proteins found in kidneys provide a striking example of this action. Although humans generate the equivalent of about 45 gal of urine a day, aquaporins ensure that most of the water is reabsorbed into the body—leaving only about a quart to be excreted.

Robert Stroud, a professor of biochemistry and biophysics at the University of California, San Francisco, calls Agre’s contributions “stellar. He discovered that aquaporins exist, showed us where they are found, predicted how they work, and related many human mutations in these proteins to specific diseases. He really deserves this prize.”

TRANSPORTED MacKinnon’s landmark structure of a potassium ion channel revealed how the protein moves K+ ions (green sphere) across cell membranes.
© 2003 RODERICK MACKINNON



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Chemical & Engineering News
Copyright © 2003 American Chemical Society



 
NOBEL PRIZE
CHEMISTRY PRIZE FOR CELL CHANNELS
Two honored for deciphering how water and ions move in and out of cells
[C&EN, Oct. 13, 2003]

MEDICINE PRIZE RECOGNIZES MRI
Chemist and physicist honored for developing powerful diagnostic tool
[C&EN, Oct. 13, 2003]

CHILLS AND THRILLS
Theories of superconductivity and superfluidity garner physics prize
[C&EN, Oct. 13, 2003]

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