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One protein, two channels:
Scientists explain mechanism in aquaporins
E. Kloeppel, Physical Sciences Editor
photo to enlarge
by L. Brian Stauffer
Tajkhorshid, a professor of biochemistry at
Illinois and a researcher at the Beckman
Institute for Advanced Science and Technology, has
identified a key component of the gating mechanism
in aquaporins that controls both the passage of
water and the conduction of ions.
CHAMPAIGN, Ill. —
Using computer simulations and experimental results, researchers at
the University of Illinois at Urbana-Champaign and the University of
Arizona have identified a key component of the gating mechanism in aquaporins
that controls both the passage of water and the conduction of ions.
Aquaporins are a class of proteins that form membrane channels in cell
walls and allow for water movement between a cell and its surroundings.
A number of aquaporins, including aquaporin-1, have been found to function
as ion channels, as well.
“Understanding the molecular mechanism behind gating in membrane
channels could lead to more effective protein engineering,” said
Emad Tajkhorshid, a professor of biochemistry at Illinois and a researcher at the Beckman
Institute for Advanced Science and Technology.
In work funded by the National Institutes of Health, Tajkhorshid and
co-workers show that the same protein can be used as a water channel
or an ion channel depending on the signaling pathway activated in the
cell. The scientists report their findings in the September issue of
the journal Structure.
Taking advantage of the known crystal structure of aquaporin-1 and the
power of molecular dynamics simulations, the researchers explored the
central pore as a candidate pathway for conducting ions. Gating of the
central pore is controlled by cyclic guanosine monophosphate, a signaling
nucleotide inside the cell, which induces a conformational change in
one of the aquaporin loops (loop D).
“This loop is very flexible, has four positively charged arginine
residues in a row, and extends into the central pore,” Tajkhorshid
said. “We believe the cGMP interacts with loop D, facilitating
its outward motion, which triggers the opening of the gate.”
The work highlights a close interaction between simulation and experiment.
Based on their simulation results, the researchers designed a mutant
in which two arginines in loop D were replaced by two alanines. In laboratory
experiments performed at Arizona, the substitution caused an almost
complete removal of ion conduction, but had no appreciable effect on
“Knowing the mechanism gives us a new handle to control the opening
or closing of the central pore,” Tajkhorshid said. “By modifying
the pore-lining residue, or altering the length of loop D that gates
the pore, we can shut down the ion conductivity completely, or engineer
new aquaporins that can be opened more easily or have a higher ion conduction
rate once open.”
With Tajkhorshid, co-authors of the paper are Illinois graduate student
and lead author Jin Yu, University of Arizona experimentalist Andrea
J. Yool, and Illinois physicist Klaus Schulten.
Editor’s note: To reach Emad Tajkhorshid
(pronounced uh-MOD tazh-CORE-shid), call 217-244-6914; e-mail: firstname.lastname@example.org.