Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published April 2, 2010 | Supplemental Material + Accepted Version
Journal Article Open

A Gating Charge Transfer Center in Voltage Sensors

Abstract

Voltage sensors regulate the conformations of voltage-dependent ion channels and enzymes. Their nearly switchlike response as a function of membrane voltage comes from the movement of positively charged amino acids, arginine or lysine, across the membrane field. We used mutations with natural and unnatural amino acids, electrophysiological recordings, and x-ray crystallography to identify a charge transfer center in voltage sensors that facilitates this movement. This center consists of a rigid cyclic "cap" and two negatively charged amino acids to interact with a positive charge. Specific mutations induce a preference for lysine relative to arginine. By placing lysine at specific locations, the voltage sensor can be stabilized in different conformations, which enables a dissection of voltage sensor movements and their relation to ion channel opening.

Additional Information

© 2010 American Association for the Advancement of Science. Received 14 December 2009; accepted 16 February 2010. We thank members of D. Gadsby's laboratory (Rockefeller University) for assistance with oocyte preparation; members of the MacKinnon laboratory for assistance; the staff at beamline X29 (National Synchrotron Light Source, Brookhaven National Laboratory) for advice at the synchrotron; and A. Banerjee, J. A. Letts, G. von Heijne (Stockholm University), and J. Chen (Purdue University) for helpful discussions. R.M. is the Investigator in the Howard Hughes Medical Institute. D.A.D. is a George Grant Hoag Professor of Chemistry. Supported by NIH GM43949 to R.M and NS 34407 to D.A.D. The x-ray crystallographic coordinates and structure factor files have been deposited in the Protein Data Bank with accession ID 3LNM.

Attached Files

Accepted Version - nihms201352.pdf

Supplemental Material - 1.pdf

Files

nihms201352.pdf
Files (3.1 MB)
Name Size Download all
md5:271f2fc90fb0e8e476db4a1534f96691
2.4 MB Preview Download
md5:5a347e2f53e2481dfc96a3bf4f86cbbf
661.9 kB Preview Download

Additional details

Created:
August 19, 2023
Modified:
October 20, 2023