Voltage-gated K+ channel from mammalian brain: 3D structure at 18A of the complete (alpha)4(beta)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 alpha-subunits and four cytoplasmically-associated beta-subunits. The 18A resolution structure reveals an asymmetric, dumb-bell-shaped complex with 4-fold symmetry, a length of 140A and variable width. By fitting published X-ray data for recombinant components to our EM map, the modulatory (beta)(4) was assigned to the innermost 105A end, the N-terminal (T1)(4) domain of the alpha-subunit to the central 50A moiety and the pore-containing portion to the 125A 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 beta-subunits for coupling of responses to changes in excitability and metabolic status of neurons.
Orlova
Elena V
EV
Department of Biological Sciences, Imperial College of Science Technology and Medicine, London SW7 2AY, UK.
Papakosta
Marianthi
M
Booy
Frank P
FP
van Heel
Marin
M
Dolly
J Oliver
JO
D000818:Animals; D001923:Brain Chemistry; D008958:Models, Molecular; D009474:Neurons / Q000737:chemistry; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000302:isolation & purification / Q000648:ultrastructure*; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry
D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D011994:Recombinant Proteins