Crystal structure of full-length KcsA in its closed conformation

KcsA is a proton-activated, voltage-modulated K+ channel that has served as the archetype pore domain in the Kv channel superfamily. Here, we have used synthetic antigen-binding fragments (Fabs) as crystallographic chaperones to determine the structure of full-length KcsA at 3.8 angstrom, as well as that of its isolated C-terminal domain at 2.6 angstrom. The structure of the full-length KcsA-Fab complex reveals a well-defined, 4-helix bundle that projects approximate to 70 angstrom toward the cytoplasm. This bundle promotes a approximate to 15 degrees bending in the inner bundle gate, tightening its diameter and shifting the narrowest point 2 turns of helix below. Functional analysis of the full-length KcsA-Fab complex suggests that the C-terminal bundle remains whole during gating. We suggest that this structure likely represents the physiologically relevant closed conformation of KcsA.