Meeting Date: Saturday, November 4, 2017 Abstract deadline is October 23, 2017 Registration deadline is October 27, 2017 You can
Johns Hopkins University Research Discovery Awards “In 2017, 23 Category 1 Discovery Awards and 3 Category 2 Discovery Awards were given
“VirulenceFactors and Host Defenses to Viral Infection”
“Designing brighter dyes for advanced fluorescencemicroscopy”
Jesse Yoder from the Amzel lab will present the talk titled “A Tail of Two Channels: Regulation of Sodium Channels Nav1.4 and Nav1.5 by Ca2+ and Calmodulin”
Voltage-gated sodium channels (Nav) account for the action potential upstroke in all excitable tissues: neurons, cardiac and skeletal muscle. Nav1.4, the skeletal muscle isoform, responds to high Ca2+ with a rapid calmodulin (CaM) and calcium-dependent inactivation (CCDI) that substantially reduces Na+ current. The mechanistic details of how this inactive state reflects the conformational of CaM bound to the channel are unknown. Here we report two crystal structures of Nav1.4 C-terminal domain (CTerm) bound to CaM, in the presence (3.3 Å resolution) and absence (1.8 Å resolution) of Ca2+, along with binding data and a novel thermodynamic model of CaM’s response to Ca2+ when bound to Nav1.4 and Nav1.5 (the cardiac muscle isoform). Together these two structures and the thermodynamic model point towards the mechanism of CCDI regulation in Nav1.4. We show that the C-lobe of CaM stays anchored on the IQ motif, regardless of Ca2+ level, while the N-lobe acts as the “switch” at high Ca2+ levels by changing conformation and seeking a new binding partner. A short discussion on molecular replacement methods developed for this project will also be presented at the end of the talk.
University of California Santa Barbara