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of 0.837). The loops between helices 3 and 4 and the C-terminus are
distinguished by their enhanced mobilities.
A clearer picture of the relative mobilities of the different structural
components in the long-time regime is obtained upon examination of the slowest
mode profile obtained by GNM in Fig. 7.5 (panels B and C). The slowest mode
divides the structure into two regions subject to anticorrelated fluctuations.
Mainly, the positive and negative portions of the mode 1 eigenvector plotted in
Fig. 7.5C
define the two anticorrelated regions. The cross-over regions between
them form the minima in the square displacements profile shown in Fig
. 7
.5B.
The corresponding residues occupy central positions in the TM helices
(Fig. 7.5D). Since they also lie at the interface between the two anticorrelated
regions of the molecule, these residues play an important role in transmitting
conformational perturbations. Many residues lying in this critical region (e.g.,
D83, V162, F261) participate in the retinal binding pocket, and efficiently
propagate local conformational changes between the CP and extracellular (EC)
ends of the molecule (Isin
et al.
, 2006). ANM analysis shows that this mode
essentially drives a global twisting of the TM helices, which results in an overall
expansion at the two ends. These conformational changes agree well with
experimental data (Isin
et al.
, 2006). In particular, the mobility of spin-labeled
side chains at the buried surfaces of TM helices 1, 2, 3, 6 and 7 were found to
increase upon isomerization, indicating a reduced packing consistent with the
expansion of the pore, in accord with ANM results.
Mechanosensitive Channel (MscL): Channel widening upon global twisting
and torsion
.
These proteins act as a “safety-valve” in
E. Coli
: they open up
when the osmotic pressure is beyond a certain threshold (Hamill & Martinac,
2001; Anishkin & Kung, 2005), thus preventing membrane breakdown and
cell lysis. The diameter of the gate region, as inferred from the X-ray structure
of the closed form (Chang
et al.
, 1998), is ~2 Å, whereas in the open form it is
~30-35 Å (Sukharev
et al.
, 1999), suggesting a significant conformational
change. ENM studies have elucidated the dynamics of this mechanosensitive
protein (Valadie
et al.
, 2003; Haliloglu & Ben-Tal, 2008). Two major kinds of
motions were identified: Type I (Fig. 7.6), a symmetrical motion that corresponds
to an overall iris-like opening, exhibited by the non-degenerate modes; and Type
II, which resulted in a global bending/tilting. Notably, three non-degenerate
modes (modes 11, 31 and 64) (Valadie
et al.
, 2003) accessible to the closed state
can alone account for 65% of the conformational change observed between the
closed and open states, while the first 100 modes describe 76% of the transition.
As to the opposite change, five non-degenerate modes recover 65% of the
