4DCK

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

4DCK の概要

• エントリーDOI: 10.2210/pdb4dck/pdb
• 分子名称: Sodium channel protein type 5 subunit alpha, Calmodulin, Fibroblast growth factor 13, ... (5 entities in total)
• 機能のキーワード: 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
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane; Multi-pass membrane protein: Q14524; Cytoplasm, cytoskeleton, spindle: P62158
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 57904.94

構造登録者

Chung, B.C.,Wang, C.,Yan, H.,Pitt, G.S.,Lee, S.Y. (登録日: 2012-01-17, 公開日: 2012-06-27, 最終更新日: 2024-02-28)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.2 Å)