Calcium Channel α2δ Subunits—Structure and Gabapentin Binding

• DOI: 10.1124/mol.59.5.1243
• Publication Date: 2018-01-08T20:42:33Z
• Authors: Elsé Marais; Norbert Klugbauer; Franz Hofmann
• Keywords: Mice, Inbred BALB C; 0303 health sciences; Binding Sites; Cyclohexanecarboxylic Acids; Sequence Homology, Amino Acid; Protein Conformation; Molecular Sequence Data; Acetates; Transfection; Mice; 03 medical and health sciences; COS Cells; Animals; Amino Acid Sequence; Calcium Channels; Amines; Gabapentin; Excitatory Amino Acid Antagonists; gamma-Aminobutyric Acid

High-voltage activated calcium channels are modulated by a series of auxiliary proteins, including those the α₂δ family. Until recently, only single subunit was known, but two further members, α₂δ-2 and -3, have since been identified. In this study, structure these novel subunits has characterized binding antiepileptic drug gabapentin investigated. Using antibodies directed against amino terminal portion gross could be analyzed Western blotting. Similar to α₂δ-1, both -3 consist proteins—a larger α₂ smaller δ that can separated reduction. The also highly <i>N</i>-glycosylated with approximately 30 kDa their mass consisting oligosaccharides. α₂δ-1 detected in all mouse tissues studied, whereas found at high levels brain heart. α₂δ-3 observed brain. α₂δ-2, not α₂δ-3, were bind gabapentin. The<i>K</i>_d value 153 nM compared higher affinity (<i>K</i>_d = 59 nM).