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Figure 7.
Figure 7. A schematic model of GHR activation. The hormone is
depicted in blue ribbon style and JAK2 as ellipses. The first
diagram shows the unliganded preformed hGHR dimer on the plasma
membrane with the subunits sitting equivalently. In the center
diagram, a hormone molecule binds via site 1 to the left-hand
receptor molecule (receptor 1). This is the structure observed
in the published 1:1 complex. The dimerization domains of each
receptor (located in the C-terminal domains) are far from
complementary because of charge repulsions and steric clashes.
The right-hand diagram shows the structure as observed in the
crystal structure of the published 2:1 complex. On binding to
site 2 of the hormone, the second receptor molecule must move
with respect to the first molecule so that the dimerization
contacts are optimized, involving a rotation and a vertical
movement. This then causes a rotation of the TMD and
juxtamembrane regions, resulting in rotation and activation by
transphosphorylation of the JAK2 molecules bound to box 1, and
the initiation of the GHR signaling cascade. The red line
indicates disulfide bond formation by Cys241, which occurs as a
result of receptor activation28. See also
http://www2.imb.uq.edu.au/groups/waters/hghr.html.
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