Molecular Coupling of S4 to a K+ Channel's Slow Inactivation Gate
Journal Article
·
· Journal of General Physiology
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Biosciences Division. Dept. of Molecular and Cell Biology; DOE/OSTI
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Biosciences Division. Dept. of Molecular and Cell Biology
The mechanism by which physiological signals regulate the conformation of molecular gates that open and close ion channels is poorly understood. Voltage clamp fluorometry was used to ask how the voltage-sensing S4 transmembrane domain is coupled to the slow inactivation gate in the pore domain of the Shaker K+ channel. Fluorophores attached at several sites in S4 indicate that the voltage-sensing rearrangements are followed by an additional inactivation motion. Fluorophores attached at the perimeter of the pore domain indicate that the inactivation rearrangement projects from the selectivity filter out to the interface with the voltage-sensing domain. Some of the pore domain sites also sense activation, and this appears to be due to a direct interaction with S4 based on the finding that S4 comes into close enough proximity to the pore domain for a pore mutation to alter the nanoenvironment of an S4-attached fluorophore. We propose that activation produces an S4–pore domain interaction that disrupts a bond between the S4 contact site on the pore domain and the outer end of S6. Our results indicate that this bond holds the slow inactivation gate open and, therefore, we propose that this S4-induced bond disruption triggers inactivation.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
- Sponsoring Organization:
- National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
- Grant/Contract Number:
- AC02-05CH11231
- OSTI ID:
- 1625205
- Journal Information:
- Journal of General Physiology, Journal Name: Journal of General Physiology Journal Issue: 5 Vol. 116; ISSN 0022-1295
- Publisher:
- Rockefeller University PressCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Similar Records
Coupling sensor to enzyme in the voltage sensing phosphatase
Structural basis for severe pain caused by mutations in the S4-S5 linkers of voltage-gated sodium channel NaV1.7
Mechanism of Cd[superscript 2+] Coordination during Slow Inactivation in Potassium Channels
Journal Article
·
Mon Jul 29 20:00:00 EDT 2024
· Nature Communications
·
OSTI ID:2470965
Structural basis for severe pain caused by mutations in the S4-S5 linkers of voltage-gated sodium channel NaV1.7
Journal Article
·
Wed Mar 29 20:00:00 EDT 2023
· Proceedings of the National Academy of Sciences of the United States of America
·
OSTI ID:2423635
Mechanism of Cd[superscript 2+] Coordination during Slow Inactivation in Potassium Channels
Journal Article
·
Tue Oct 09 00:00:00 EDT 2012
· Structure
·
OSTI ID:1048957