Jefferson scientists uncover new clues to how crucial molecular gatekeepers work

ormal resting state.

The more recent and controversial theory proposed by Nobel laureate Roderick MacKinnon of Rockefeller University holds that a kind of molecular paddle comprised of the S4 segment and part of the S3 segment moves through the cell membrane, carrying S4's positive charges with it across the lipid. As in the conventional theory, the S4 movement controls the channel's opening and closing. The two theories differ in part because the paddle must move its positive charges all the way across the cell membrane. The conventional theory says that charges move a short distance through the gating pore.

In the current work, Dr. Horn and colleague Christopher Ahern, Ph.D., a research assistant in the Department of Physiology at Jefferson Medical College, showed that the field through which the voltage sensor's charges moved is very short, lending support to the conventional model.

"Using a molecular tape measure with a very fine resolution 1.24 Angstroms we tethered charges to the voltage sensor," Dr. Horn explains. "When the tether is too long, the voltage sensor can't pull it through the electric field," meaning the electric field is highly focused.

"This is another nail in the coffin of the paddle model," he says, "because the thickness of the electric field is much smaller than predicted by that model. The measurement is unambiguous in terms of the relationship between length of the tether and how much charge gets pulled through the electric field.

Next, the researchers are tackling the relationship between S4's movement and the gates that open and close the channels.



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