4JQ0

Voltage-gated sodium channel 1.5 C-terminal domain in complex with FGF12B and Ca2+/calmodulin

Summary for 4JQ0

• Entry DOI: 10.2210/pdb4jq0/pdb
• Related: 4JPZ
• Descriptor: Fibroblast growth factor 12, Calmodulin, Sodium channel protein type 5 subunit alpha, ... (4 entities in total)
• Functional Keywords: ef hand, ion channel, membrane, transport protein
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane ; Multi-pass membrane protein : P61328; Nucleus : P62158; Cytoplasm, cytoskeleton, spindle : Q14524
• Total number of polymer chains: 3
• Total formula weight: 66287.82

Authors

Wang, C.,Chung, B.C.,Yan, H.,Wang, H.G.,Lee, S.Y.,Pitt, G.S. (deposition date: 2013-03-19, release date: 2014-05-21, Last modification date: 2024-02-28)

Primary citation

Wang, C.,Chung, B.C.,Yan, H.,Wang, H.G.,Lee, S.Y.,Pitt, G.S.
Structural analyses of Ca(2+)/CaM interaction with NaV channel C-termini reveal mechanisms of calcium-dependent regulation.
Nat Commun, 5:4896-4896, 2014

PubMed Abstract: Ca(2+) regulates voltage-gated Na(+) (NaV) channels, and perturbed Ca(2+) regulation of NaV function is associated with epilepsy syndromes, autism and cardiac arrhythmias. Understanding the disease mechanisms, however, has been hindered by a lack of structural information and competing models for how Ca(2+) affects NaV channel function. Here we report the crystal structures of two ternary complexes of a human NaV cytosolic C-terminal domain (CTD), a fibroblast growth factor homologous factor and Ca(2+)/calmodulin (Ca(2+)/CaM). These structures rule out direct binding of Ca(2+) to the NaV CTD and uncover new contacts between CaM and the NaV CTD. Probing these new contacts with biochemical and functional experiments allows us to propose a mechanism by which Ca(2+) could regulate NaV channels. Further, our model provides hints towards understanding the molecular basis of the neurologic disorders and cardiac arrhythmias caused by NaV channel mutations.

PubMed: 25232683
DOI: 10.1038/ncomms5896

Experimental method

X-RAY DIFFRACTION (3.84 Å)