CONTACT: L. E. OHMAN
283 Medical Laboratories
Iowa City IA 52242
(319) 335-6660; fax (319) 335-8034
UI researcher identifies a mechanism that controls protein activity
IOWA CITY, Iowa -- Proteins are responsible for everything from producing
cell and organ structure to providing the body with nutrition. Careful
regulation of their activity helps maintain essential actions such as a
regular heartbeat, proper lung function, and communication among brain
A mechanism that regulates protein activity, previously undescribed
for advanced cells, has been reported by Dr. Toshinori Hoshi, University
of Iowa assistant professor of physiology and biophysics.
The mechanism involves adding an oxygen molecule to methionine, an amino
acid, in a process called oxidation. Oxidation drastically changes the
way methionine interacts with its environment. The regular action of methionine
is restored in a process called reduction. Unlike other amino acids, the
methionine reduction, or restoration, process is carefully controlled by
an enzyme. This enzyme is called MsrA.
Hoshi hypothesized that the tight control of the oxidation-reduction
process in methionine might make it an important regulatory mechanism for
various body functions. To test this idea, he looked at the effect methionine
oxidation and reduction had on potassium channels.
Potassium channels work in the classic ball-and-chain model of opening
and closing where a ball-like structure physically occludes the channel
pore, closing it. Using the patch-clamp technique in combination with recombinant
DNA techniques, Hoshi and his colleagues found that the oxidation and reduction
of methionine did affect potassium channel activity. They found that the
channel stayed open when the methionine was oxidated and closed with reduction
of the amino acid. These findings are published in the September issue
of the Proceedings of the National Academy of Sciences.
Hoshi thinks that these results show that the methionine oxidation-reduction
process plays an important role in the regulation of potassium channels.
But, he believes the regulatory mechanism plays a bigger role in body function.
"We used the potassium channels as a model to show the importance
of methionine oxidation," he says. "I think it is important for
every cell, and may work on all proteins, not just cell channels."
Potential importance of these findings expands beyond cell activity
to cell death. There is a suggestion that methionine oxidation is involved
Alzheimer's disease and aging.
"Active cells produce free radicals, molecules known to damage
cells, and the enzyme, MsrA, eliminates the damage done by free radicals,"
Therefore, it is likely that the methionine oxidation and reduction
process has antioxidant properties.
Hoshi and his colleagues are now investigating how methionine oxidation
is involved in a wide variety of physiological processes, such as learning,
memory and aging.