The Structure of the Potassium Channel: Molecular Basis of K ⁺ Conduction and Selectivity

Abstract

The potassium channel from Streptomyces lividans is an integral membrane protein with sequence similarity to all known K+ channels, particularly in the pore region. X-ray analysis with data to 3.2 angstroms reveals that four identical subunits create an inverted teepee, or cone, cradling the selectivity filter of the pore in its outer end. The narrow selectivity filter is only 12 angstroms long, whereas the remainder of the pore is wider and lined with hydrophobic amino acids. A large water-filled cavity and helix dipoles are positioned so as to overcome electrostatic destabilization of an ion in the pore at the center of the bilayer. Main chain carbonyl oxygen atoms from the K+ channel signature sequence line the selectivity filter, which is held open by structural constraints to coordinate K+ ions but not smaller Na+ ions. The selectivity filter contains two K+ ions about 7.5 angstroms apart. This configuration promotes ion conduction by exploiting electrostatic repulsive forces to overcome attractive forces between K+ ions and the selectivity filter. The architecture of the pore establishes the physical principles underlying selective K+ conduction.

The Impact of Heterozygous KCNK3 Mutations Associated With Pulmonary Arterial Hypertension on Channel Function and Pharmacological Recovery

“…G203D KCNK3 disrupts the conserved “GxG” potassium selectivity filter amino acid sequence in 1 of the channel's 2 pore‐loop domains, a region sensitive to dominant‐negative mutations 24, 25, 26. We first engineered and studied the WT‐G203D KCNK3 heterodimer (Figure 7B, left), and indeed observed severe dominant‐negative dysfunction, as the mutant channels produced small currents across pH 6.4 through 10.4 (Figure 7B and 7C; also see Figure S4).…”

Molecular basis of ion permeability in a voltage‐gated sodium channel

“…In potassium channels, the binding sites are formed by polypeptide backbone carbonyl groups (Doyle et al , 1998), whereas in the NavMs sodium channel the SF is lined with amino acid side chains (Fig 4). Potassium ions are fully dehydrated in potassium channel SFs and form direct contacts with the polypeptide.…”

S4 Charges Move Close to Residues in the Pore Domain during Activation in a K Channel

“…The central part of the ion channel (from the fifth to the sixth transmembrane segments, S5–S6) contains the pore and several of the gates, and is most likely similar to the structurally determined bacterial KcsA K channel (Doyle et al 1998; MacKinnon et al 1998). The voltage sensing part of the ion channel (S1–S4) is located peripherally to the central pore (Li-Smerin et al 2000).…”

“…The structure of the KcsA channel has been used as a template when constructing this cartoon, keeping the distances between residues as in the KcsA channel (Doyle et al 1998). S4 is shown with solid lines in the activated state and dashed lines in the resting state.…”