Geometry and Topology of Folding Landscapes - Biological Networks - page 144

Fig. 7.2. Sequence and structure of the pore region of five structurally known potassium
channels. (a) Alignment of the pore region sequences. The regions corresponding to the helices
TM1 and TM2 and the selectivity filter are indicated by yellow, blue and red blocks, respectively.
The alignment was performed using ClustalW (Thompson et al. , 1994). Fully or highly conserved
regions are shown in bold. The signature motif GYG at the selectivity filter, is highlighted and
shaded in red (b) Structural comparison of the pore forming regions of the K + channels aligned in
panel a. These are all tetrameric structures, the monomers of which contain either 2 TM helices
(KcsA, MthK and KirBac) colored yellow (TM1) and blue (TM2), or 6 TM helices (KvAP and
Shaker) denoted as S1-S6. Only the pore forming helices S5 and S6, equivalent to TM1 and TM2,
are displayed here, along with the selectivity filter, (which is colored red in all the structures).
profile along the selectivity filter (Bernèche & Roux, 2003). Yet, a fundamental
question that remained unanswered until recently has been the mechanism of
gating , i.e., the conformational events that allow for the transfer of ions from the
central cavity to the CP region through the channel-pore. In the X-ray structures,
the radius of the pore is too small to let the ions through. The question was: how
does the narrow pore open up to permit the permeation of potassium ions?
Toward gaining an understanding of the potential mechanism of pore
opening, we recently examined five K + channels, KcsA, KirBac, MthK, KvAP
and Shaker (Shrivastava & Bahar, 2006). Figure 7.2a shows a comparison of the