Fig. 1.28 The blooming and twisting components of the isomerization underlying gating in pLGICs. The
model is a composite of data obtained on GLIC and GluCl. (A) The blooming transition. The conformation
of the A state as captured by the X-ray structure of GLIC at pH 4 (Sauguet et al. 2013) is shown in a cartoon
representation in light gray with the C-loop closed on top of the orthosteric site in darker gray. For
illustration, a hypothetical agonist bound to the extracellular domain is shown as green spheres; its
coordinates correspond to those of L-glutamate in the active state of GluCl (Hibbs and Gouaux 2011)
after optimal superposition of the TM regions of GLIC and GluCl. The position of the extracellular βsandwiches in the resting state of pLGICs is shown in pink; coordinates were extracted from the crystal
structure of GLIC pH 7 (Sauguet et al. 2014) and are shown after optimal superposition of the TM regions.
The pink dashed arrows illustrate the direction of the blooming motion from the active to the resting state.
The blooming transition results in a significant reshaping of the extracellular subunit/subunit interfaces,
which open the orthosteric site and presumably reduce the affinity for the agonist. (B) The twisting
transition. The conformation of the active state of pLGICs as captured by the X-ray structure of GluCl
in complex with the allosteric agonist ivermectin (Hibbs and Gouaux 2011) is shown in light gray.
Ivermectin bound at the subunit interfaces in the TM domain is shown as magenta sticks. The orientation
of the extracellular β-sandwiches captured at the end of the twisting transition by molecular dynamics
simulations of GluCl with ivermectin removed (Calimet et al. 2013) is shown in cyan; the coordinates of
the channel taken after 100-ns relaxation without ivermectin are shown after optimal superposition of the
TM regions. The blue arrow illustrates the direction of the twisting transition from the active (untwisted) to
the resting (twisted state) (From Taly et al. 2014. See also Fig. 1.33).
40
1 Membrane Proteins and Their Natural Environment
model is a composite of data obtained on GLIC and GluCl. (A) The blooming transition. The conformation
of the A state as captured by the X-ray structure of GLIC at pH 4 (Sauguet et al. 2013) is shown in a cartoon
representation in light gray with the C-loop closed on top of the orthosteric site in darker gray. For
illustration, a hypothetical agonist bound to the extracellular domain is shown as green spheres; its
coordinates correspond to those of L-glutamate in the active state of GluCl (Hibbs and Gouaux 2011)
after optimal superposition of the TM regions of GLIC and GluCl. The position of the extracellular βsandwiches in the resting state of pLGICs is shown in pink; coordinates were extracted from the crystal
structure of GLIC pH 7 (Sauguet et al. 2014) and are shown after optimal superposition of the TM regions.
The pink dashed arrows illustrate the direction of the blooming motion from the active to the resting state.
The blooming transition results in a significant reshaping of the extracellular subunit/subunit interfaces,
which open the orthosteric site and presumably reduce the affinity for the agonist. (B) The twisting
transition. The conformation of the active state of pLGICs as captured by the X-ray structure of GluCl
in complex with the allosteric agonist ivermectin (Hibbs and Gouaux 2011) is shown in light gray.
Ivermectin bound at the subunit interfaces in the TM domain is shown as magenta sticks. The orientation
of the extracellular β-sandwiches captured at the end of the twisting transition by molecular dynamics
simulations of GluCl with ivermectin removed (Calimet et al. 2013) is shown in cyan; the coordinates of
the channel taken after 100-ns relaxation without ivermectin are shown after optimal superposition of the
TM regions. The blue arrow illustrates the direction of the twisting transition from the active (untwisted) to
the resting (twisted state) (From Taly et al. 2014. See also Fig. 1.33).
40
1 Membrane Proteins and Their Natural Environment