Close spatial relationship between gating-sensitive amino acids in the outer and the inner vestibule of K+ channel crystal structures. Shown are two of the four subunits of the published structures of KcsA (bacterial, non-voltage gated; Protein Data Bank code 1BL8 (1)) and mammalian, voltage gated (KV1.2, Protein Data Bank Protein Data Bank code 2A79 (61)). For clarity, protein backbone ribbons are colored differently for each subunit. Key amino acid side chains are shown as van der Waals spheres (blue, amino acid at position equivalent to site 1575 in rNaV1.4; rose, amino acid at the inner turn of the P-loop, possible equivalent to Lys-1237 in rNaV1.4; green, amino acid for which a major interaction with the P-loop is proposed to account for C-type inactivation in KcsA (9). A, KcsA; Thr-74 of one subunit (P-loop; yellow ribbon) is in close relationship to Met-96 (TM2) of the adjacent subunit (white ribbon) and with Phe-103 (TM2) of the same subunit. B, KV1.2; Thr-373 of one subunit (yellow ribbon) is close to Ala-395 of the adjacent subunit (white ribbon) and to Ile-402 of the same subunit.