@article{3f3b939078e64837aaf604a7f8320063,
title = "Regulation of the NaV 1.5 cytoplasmic domain by calmodulin",
abstract = "Voltage-gated sodium channels (Nav) underlie the rapid upstroke of action potentials in excitable tissues. Binding of channel-interactive proteins is essential for controlling fast and long-term inactivation. In the structure of the complex of the carboxy-terminal portion of Nav 1.5 (CTNav 1.5) with calmodulin (CaM)-Mg2+ reported here, both CaM lobes interact with the CTNav 1.5. On the basis of the differences between this structure and that of an inactivated complex, we propose that the structure reported here represents a non-inactivated state of the CTNav', that is, the state that is poised for activation. Electrophysiological characterization of mutants further supports the importance of the interactions identified in the structure. Isothermal titration calorimetry experiments show that CaM binds to CTNav 1.5 with high affinity. The results of this study provide unique insights into the physiological activation and the pathophysiology of Nav channels.",
author = "Gabelli, {Sandra B.} and Agedi Boto and Kuhns, {Victoria Halperin} and Bianchet, {Mario A.} and Federica Farinelli and Srinivas Aripirala and Jesse Yoder and Jean Jakoncic and Tomaselli, {Gordon F.} and Amzel, {L. Mario}",
note = "Funding Information: This work was funded in part by NIH HL050411. Use of the Advanced Photon Source at Argonne National Laboratory was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. Use of the Lilly Research Laboratories Collaborative Access Team beamline at Sector 31 of the Advanced Photon Source was provided by Eli Lilly Company, which operates the facility. Data collection was carried out at beamline X6A, funded by the National Institute of General Medical Sciences, National Institute of Health under agreement GM-0080. The NSLS, Brookhaven National Laboratory is supported by the US Department of energy under contract No. DE AC02-98CH10886. We acknowledge the use and services of the JHU SOM Mass Spectrometry and Proteomics Core, supported by the NHI NIDDK center grant P30 DK089502. The rendition of Fig. 8 was contributed by T. Phelps, M.S. Publisher Copyright: {\textcopyright} 2014 Macmillan Publishers Limited. All rights reserved.",
year = "2014",
doi = "10.1038/ncomms6126",
language = "English (US)",
volume = "5",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}