UCSF

Gabapentinoid drugs for pain and anxiety act on the Ca_Vα₂δ-1 and Ca_Vα₂δ-2 subunits of high-voltage-activated calcium channels (Ca_V1s and Ca_V2s). Here we present the cryo-EM structure of the gabapentin-bound brain and cardiac Ca_V1.2/Ca_Vβ₃/Ca_Vα₂δ-1 channel. The data reveal a binding pocket in the Ca_Vα₂δ-1 dCache1 domain that completely encapsulates gabapentin and define Ca_Vα₂δ isoform sequence variations that explain the gabapentin binding selectivity of Ca_Vα₂δ-1 and Ca_Vα₂δ-2.