Sandbox Reserved 1703: Difference between revisions

Upon binding of the PAM, helix VI is shifted downward in the TMD. This downward shift induces a reorientation of the TMD from its original TM3-TM4 asymmetric dimer interface in the inactive form to an <scene name='90/904308/Active_7_tm_transparent/1'>asymmetric TM6-TM6 interface</scene>. The downward shift of helix VI is crucial for the receptor’s transformation from the inactive to the active form for 2 main reasons: (1) reorientation breaks key interactions in the TMD that stabilize the inactive form and (2) repositioning <scene name='90/904308/Active_structure/4'>intracellular loops</scene> of in the TMD to assist in the binding and recognitions of the <scene name='90/904308/G-protein/1'>G-Protein</scene>. The G-protein is made up of three subunits: <scene name='90/904308/Alpha_subunit/1'>α-subunit</scene>, <scene name='90/904308/Beta_subunit/1'>β-subunit</scene>, and a <scene name='90/904308/Gamma_subunit/1'>γ-subunit</scene>.

Transition to the active state also reorients helix 3 in both monomers to enable binding to the G-protein: Yet only one chain is required for full receptor activation. The intracellular region of helix 3 contributes the main interactions with the α-subunit of the G-protein. Intracellular Loop 2 also builds a polar interaction network with the G-protein through its ionic interactions with the <scene name='90/904308/Binding_recognition_site/2'> α-subunit</scene> of the G-protein. The ionic interactions formed further destabilize the inactive conformation<ref name="Lin"/>.