4DCK

Crystal structure of the C-terminus of voltage-gated sodium channel in complex with FGF13 and CaM

Summary for 4DCK

• Entry DOI: 10.2210/pdb4dck/pdb
• Descriptor: Sodium channel protein type 5 subunit alpha, Calmodulin, Fibroblast growth factor 13, ... (5 entities in total)
• Functional Keywords: iq-motif, ef-hand, voltage-gated sodium channel regulation, nav1.5 ctd binds to fgf13 and cam. cam binds to ca2+., transport protein-transport protein regulator-signaling protein complex, transport protein-signaling protein complex, transport protein/signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Multi-pass membrane protein: Q14524; Cytoplasm, cytoskeleton, spindle: P62158
• Total number of polymer chains: 3
• Total formula weight: 57904.94

Authors

Chung, B.C.,Wang, C.,Yan, H.,Pitt, G.S.,Lee, S.Y. (deposition date: 2012-01-17, release date: 2012-06-27, Last modification date: 2024-02-28)

Primary citation

Wang, C.,Chung, B.C.,Yan, H.,Lee, S.Y.,Pitt, G.S.
Crystal Structure of the Ternary Complex of a NaV C-Terminal Domain, a Fibroblast Growth Factor Homologous Factor, and Calmodulin.
Structure, 20:1167-1176, 2012

PubMed Abstract: Voltage-gated Na⁺ (Na(V)) channels initiate neuronal action potentials. Na(V) channels are composed of a transmembrane domain responsible for voltage-dependent Na⁺ conduction and a cytosolic C-terminal domain (CTD) that regulates channel function through interactions with many auxiliary proteins, including fibroblast growth factor homologous factors (FHFs) and calmodulin (CaM). Most ion channel structural studies have focused on mechanisms of permeation and voltage-dependent gating but less is known about how intracellular domains modulate channel function. Here we report the crystal structure of the ternary complex of a human Na(V) CTD, an FHF, and Ca²⁺-free CaM at 2.2 Å. Combined with functional experiments based on structural insights, we present a platform for understanding the roles of these auxiliary proteins in Na(V) channel regulation and the molecular basis of mutations that lead to neuronal and cardiac diseases. Furthermore, we identify a critical interaction that contributes to the specificity of individual Na(V) CTD isoforms for distinctive FHFs.

PubMed: 22705208
DOI: 10.1016/j.str.2012.05.001

Experimental method

X-RAY DIFFRACTION (2.2 Å)