Figure 2. The S6 activation gate sequence differs from the Shaker-like Kv family consensus in evolutionarily independent regulatory subunit groups. (A) Cartoon showing the PD of two diagonally opposed subunits of a closed Shaker-like Kv channel tetramer with the location of a six–amino acid sequence (PVPVIV) comprising the S6 gating hinge and activation gate overlaid to show its approximate location at the intracellular side of the conduction pathway. (B) S6 consensus sequence logo constructed from all 27 mouse and sea anemone (N. vectensis) Shaker-like Kv family subunits that can form functional homotetrameric channels. The hinge and activation gate are boxed with a red outline, and positions 1–6 as used in the paper are indicated. A highly conserved section of S6 upstream of the gate is also shown in the logo. Amino acid frequency is encoded in letter height, and colors are used to depict amino acid class (blue, hydrophobic; green, hydrophilic; magenta, proline; black, aromatic; orange, acidic; purple, basic). Note the conservative substitution V2I and V4I are found in mouse Kv2.1 and Kv2.2 and are typical for the Kv2 subfamily. (C) A similar sequence logo constructed from 43 mouse and sea anemone Shaker-like Kv regulatory subunits shows degeneration of the gate PVPVIV consensus sequence; only P1 is found in a majority of regulatory subunits. (D) Sequence logo for nine mouse Kv2 subfamily regulatory subunits with a common evolutionary origin (Kv6.1-6.4, Kv8.1-8.2, Kv9.1-9.3). Asterisks mark positions with unusual substitutions in at least some members of the group. Note the loss of P3 (hydroxyl typical) and V6 (aromatic typical) across the group. (E–K) Sequence logos broken out for seven additional evolutionarily independent groups of mouse and sea anemone regulatory subunits. Each separate group of regulatory subunits has a distinct pattern of unusual gate substitutions, marked by asterisks. Accession numbers and sequences for channels used to make the sequence logos in B–E are given in Supplemental Table 1, and amino acid frequencies at each gate position are given in Supplemental Table 2.
Figure 2.

The S6 activation gate sequence differs from the Shaker-like Kv family consensus in evolutionarily independent regulatory subunit groups. (A) Cartoon showing the PD of two diagonally opposed subunits of a closed Shaker-like Kv channel tetramer with the location of a six–amino acid sequence (PVPVIV) comprising the S6 gating hinge and activation gate overlaid to show its approximate location at the intracellular side of the conduction pathway. (B) S6 consensus sequence logo constructed from all 27 mouse and sea anemone (N. vectensis) Shaker-like Kv family subunits that can form functional homotetrameric channels. The hinge and activation gate are boxed with a red outline, and positions 1–6 as used in the paper are indicated. A highly conserved section of S6 upstream of the gate is also shown in the logo. Amino acid frequency is encoded in letter height, and colors are used to depict amino acid class (blue, hydrophobic; green, hydrophilic; magenta, proline; black, aromatic; orange, acidic; purple, basic). Note the conservative substitution V2I and V4I are found in mouse Kv2.1 and Kv2.2 and are typical for the Kv2 subfamily. (C) A similar sequence logo constructed from 43 mouse and sea anemone Shaker-like Kv regulatory subunits shows degeneration of the gate PVPVIV consensus sequence; only P1 is found in a majority of regulatory subunits. (D) Sequence logo for nine mouse Kv2 subfamily regulatory subunits with a common evolutionary origin (Kv6.1-6.4, Kv8.1-8.2, Kv9.1-9.3). Asterisks mark positions with unusual substitutions in at least some members of the group. Note the loss of P3 (hydroxyl typical) and V6 (aromatic typical) across the group. (E–K) Sequence logos broken out for seven additional evolutionarily independent groups of mouse and sea anemone regulatory subunits. Each separate group of regulatory subunits has a distinct pattern of unusual gate substitutions, marked by asterisks. Accession numbers and sequences for channels used to make the sequence logos in B–E are given in Supplemental Table 1, and amino acid frequencies at each gate position are given in Supplemental Table 2.

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