FIGURE 4.
Schematic representation of the proposed molecular mechanism underlying the IUS state. Shown are the P-loops and the S6 segments of DII and DIV. A, the non-inactivated state is shown. Lys-1237 of DIII P-loop is located close to Ile-1575 of the DIV-S6 segment. B, mutation K1237E results in electrostatic repulsion between Glu-1237 and other negatively charged amino acids in the selectivity filter (Asp-400, Glu-755). This electrostatic repulsion gives rise to a swinging out of the DIII P-loop, resulting in an interaction between the Glu-1237 and the side chain of Ile-1575 (upper arrow). This interaction favors a conformational change of the DIV-S6 segment which gives rise to the IUS state (lower arrow).