 |
|
 |
Functioning of ionic channels.
Ion channels act as molecular transducers,
responding to chemical, mechanical or electrical stimuli by opening
a pore to allow ionic current to flow. Work in my laboratory seeks to
clarify the transduction mechanisms of channel proteins such as the
voltage-gated Shaker potassium channel. We use patch-clamp recordings
for the sensitive measurement of single-molecule behavior, and seek
to extend the sensitivity of this method by exploiting microfabrication
technology. We also use single-particle imaging in cryo-electronmicroscopy
to obtain three-dimensional structures of membrane proteins without
the need for crystals.
Figure caption:
Perturbation of voltage sensing in Shaker
potassium channels The substitution of a hydrophobic residue (L382V,
denoted V2 in the figure) dramatically changes the voltage dependence
of channel activation in this "delayed rectifier" potassium
channel (upper panel). The mutation however has only a small effect
on the charge movement q that reflects voltage-sensitive conformational
changes in the channel protein (lower panel). These and other properties
of the V2 channel are well explained by a model in which the mutation
affects only the last in a series of steps that lead to channel opening.
The predictions of this model are shown as curves in the figure.
Recent publications:
Jiang,
Q.-X., E. C. Thrower, D. W. Chester, B. E. Ehrlich and F. J. Sigworth.
Three-dimensional
structure of the type 1 inositol 1,4,5-trisphosphate receptor at 24
A resolution. EMBO J. 21:3575-3581, 2002.
Jiang
QX, Chester DW, Sigworth FJ. Spherical
reconstruction: a method for structure determination of membrane proteins
from cryo-em images. J Struct Biol. 2001 Feb;133(2-3):119-31.
Zheng, J., Venkataramanan, L., and Sigworth, F.J. (2001). Hidden
Markov nodel analysis of intermediate gating steps associated with the
pore gate of Shaker potassium channels. J. Gen. Physiol. 2001 Nov;
118(5):547-562.
Klemic, K.G., Klemic, J.F., Reed, M.A. and Sigworth, F.J. Micromolded
PDMS planar electrode allows patch clamp electrical recordings from
cells. Biosensors and Bioelectronics 17:597-604, 2002. .
fred.sigworth@yale.edu
Visit Sigworth
Lab
|
|