Km. Ranatunga et al., Electrostatics studies and molecular dynamics simulations of a homology model of the Shaker K+ channel pore, EUR BIOPHYS, 30(4), 2001, pp. 295-303
Citations number
79
Categorie Soggetti
Biochemistry & Biophysics
Journal title
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
A homology model of the pore domain of the Shaker K+ channel has been const
ructed using a bacterial K+ channel, KcsA, as a template structure. The mod
el is in agreement with mutagenesis and sequence variability data. A number
of structural features are conserved between the two channels, including a
ring of tryptophan sidechains on the outer surface of the pore domain at t
he extracellular end of the helix bundle, and rings of acidic sidechains cl
ose to the extracellular mouth of the channel. One of these rings, that for
med by four Asp447 sidechains at the mouth of the Shaker pore, is shown by
pK(A) calculations to be incompletely ionized at neutral pH. The potential
energy profile for a K+ ion moved along the central axis of the Shaker pore
domain model selectivity filter reveals a shallow well, the depth of which
is modulated by the ionization state of the Asp447 ring. This is more cons
istent with the high cation flux exhibited by the channel in its conductanc
e value of 19 pS.