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Figure 6.
Figure 6. A mechanistic interpretation of KcsA gating. (a)
Possible mechanism of action of the E71A mutation in stabilizing
the open state. A single-subunit P-loop is shown with positions
67, 71 and 80 in stick representation. In the wild-type channel
(left), the interaction between Asp80 and Trp67 destabilizes the
conductive conformation of the filter and promotes inactivation
through an as yet unknown mechanism. Eliminating the Asp80-Glu71
carboxyl-carboxylate (E71A, right) disrupts the hydrogen bonding
network between the signature sequence (Gly-Tyr-Gly-Asp) and the
pore helix, causing an increase in Asp80 dynamics and perturbing
the Asp80-Trp67 interaction. This sharply decreases entry into
the inactivated state, stabilizing the open state. (b) Top,
cartoon representation of the structural conformation associated
with each kinetic state. Bottom, correlation of specific kinetic
transitions with KcsA single-channel behavior. Because
stationary gating is dominated by the deeply inactivated state,
single-channel openings occur mainly as a result of rare returns
from the inactivated state owing to conformational changes in
the selectivity filter while the lower gate remains open.
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