Voltage-gated K+ Channel from Mammalian Brain: 3D Structure at 18 Å of the Complete (α)4(β)4 Complex

Voltage-sensitive K+ channels (Kv) serve numerous important roles, e.g. in the control of neuron excitability and the patterns of synaptic activity. Here, we use electron microscopy (EM) and single particle analysis to obtain the first, complete structure of Kv1 channels, purified from rat brain, which contain four transmembrane channel-forming α-subunits and four cytoplasmically-associated β-subunits. The 18 Å resolution structure reveals an asymmetric, dumb-bell-shaped complex with 4-fold symmetry, a length of 140 Å and variable width. By fitting published X-ray data for recombinant components to our EM map, the modulatory (β)4 was assigned to the innermost 105 Å end, the N-terminal (T1)4 domain of the α-subunit to the central 50 Å moiety and the pore-containing portion to the 125 Å membrane part. At this resolution, the selectivity filter could not be localised. Direct contact of the membrane component with the central (T1)4 domain occurs only via peripheral connectors, permitting communication between the channel and β-subunits for coupling of responses to changes in excitability and metabolic status of neurons.