Solution NMR structure of the C-terminal EF-hand domain of human cardiac sodium channel NaV1.5.

ABSTRACT: The voltage-gated sodium channel NaV1.5 is responsible for the initial upstroke of the action potential in cardiac tissue. Levels of intracellular calcium modulate inactivation gating of NaV1.5, in part through a C-terminal EF-hand calcium binding domain. The significance of this structure is underscored by the fact that mutations within this domain are associated with specific cardiac arrhythmia syndromes. In an effort to elucidate the molecular basis for calcium regulation of channel function, we have determined the solution structure of the C-terminal EF-hand domain using multidimensional heteronuclear NMR. The structure confirms the existence of the four-helix bundle common to EF-hand domain proteins. However, the location of this domain is shifted with respect to that predicted on the

SUBMITTER: Chagot B 

PROVIDER: S-EPMC2649110 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature