4OVN

Voltage-gated Sodium Channel 1.5 (Nav1.5) C-terminal domain in complex with Calmodulin poised for activation

Summary for 4OVN

• Entry DOI: 10.2210/pdb4ovn/pdb
• Descriptor: Calmodulin, Sodium channel protein type 5 subunit alpha, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: scn5a, voltage gated sodium channel, calmodulin, metal binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 180930.14

Authors

Gabelli, S.B.,Bianchet, M.A.,Boto, A.,Jakoncic, J.,Tomaselli, G.F.,Amzel, L.M. (deposition date: 2013-12-10, release date: 2014-12-03, Last modification date: 2024-10-30)

Primary citation

Gabelli, S.B.,Boto, A.,Kuhns, V.H.,Bianchet, M.A.,Farinelli, F.,Aripirala, S.,Yoder, J.,Jakoncic, J.,Tomaselli, G.F.,Amzel, L.M.
Regulation of the NaV1.5 cytoplasmic domain by calmodulin.
Nat Commun, 5:5126-, 2014

PubMed Abstract: Voltage-gated sodium channels (Na(v)) 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 Na(v)1.5 (CTNa(v)1.5) with calmodulin (CaM)-Mg(2+) reported here, both CaM lobes interact with the CTNa(v)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 CTNa(v), 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 CTNa(v)1.5 with high affinity. The results of this study provide unique insights into the physiological activation and the pathophysiology of Na(v) channels.

PubMed: 25370050
DOI: 10.1038/ncomms6126

Experimental method

X-RAY DIFFRACTION (2.8 Å)