Crystal structure of the tetramerization domain of the Shaker potassium channel

Voltage-dependent, ion-selective channels such as Na+, Ca2+ and K+ channel proteins function as tetrameric assemblies of identical or similar subunits1,2,3,4. The clustering of four subunits is thought to create an aqueous pore5,6 centred at the four-fold symmetry axis. The highly conserved, amino-terminal cytoplasmic domain (∼130 amino acids) immediately preceding the first putative transmembrane helix S1 is designated T1. It is known to confer specificity for tetramer formation7,8, so the heteromeric assembly of K+-channel subunits is an important mechanism for the observed channel diversity9,10,11. We have determined the crystal structure of the T1 domain of a Shaker potassium channel at 1.55 Å resolution. The structure reveals that four identical subunits are arranged in a four-fold symmetry surrounding a centrally located pore about 20 Å in length. Subfamily-specific assembly is provided primarily by polar interactions encoded in a conserved set of amino acids at its tetramerization interface. Most highly conserved amino acids in the T1 domain of all known potassium channels are found in the core of the protein, indicating a common structural framework for the tetramer assembly.