Beta2 adrenergic receptor-Gs protein complex: Difference between revisions
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GPCRs bind their ligand and [[Group:SMART:A Physical Model of the β2-Adrenergic Receptor|overcome a conformational change]] that activates an attached [[Guanine nucleotide-binding protein]] (G protein) and allows it to detach from the cellular end of the receptor and start the different signal transduction pathways. | GPCRs bind their ligand and [[Group:SMART:A Physical Model of the β2-Adrenergic Receptor|overcome a conformational change]] that activates an attached [[Guanine nucleotide-binding protein]] (G protein) and allows it to detach from the cellular end of the receptor and start the different signal transduction pathways. | ||
G proteins<ref>https://en.wikipedia.org/wiki/G_protein</ref> are a family of proteins that act as molecular switches inside cells. G proteins belong to the larger group of enzymes called GTPases<ref>https://en.wikipedia.org/wiki/GTPase</ref>, and appear either as monomeric small GTPases<ref>https://en.wikipedia.org/wiki/Small_GTPase</ref>, or as heterotrimeric G protein complexes<ref>https://en.wikipedia.org/wiki/Heterotrimeric_G_protein</ref> that are made up of alpha (α), beta (β) and gamma (γ) subunits<ref>doi:10.1093/dnares/7.2.111</ref>. When they are bound to guanosine triphosphate ([https://en.wikipedia.org/wiki/Guanosine_triphosphate GTP]), they are 'on', and when they are bound to guanosine diphosphate ([https://en.wikipedia.org/wiki/Guanosine_diphosphate GDP]), they are 'off' | G proteins<ref>https://en.wikipedia.org/wiki/G_protein</ref> are a family of proteins that act as molecular switches inside cells. G proteins belong to the larger group of enzymes called GTPases<ref>https://en.wikipedia.org/wiki/GTPase</ref>, and appear either as monomeric small GTPases<ref>https://en.wikipedia.org/wiki/Small_GTPase</ref>, or as heterotrimeric G protein complexes<ref>https://en.wikipedia.org/wiki/Heterotrimeric_G_protein</ref> that are made up of alpha (α), beta (β) and gamma (γ) subunits<ref>doi:10.1093/dnares/7.2.111</ref>. When they are bound to guanosine triphosphate ([https://en.wikipedia.org/wiki/Guanosine_triphosphate GTP]), they are 'on', and when they are bound to guanosine diphosphate ([https://en.wikipedia.org/wiki/Guanosine_diphosphate GDP]), they are 'off'. | ||
Since these receptors have seven transmembrane helices as well as inner and outer cell regions, they are very difficult to purify and crystalize. Some crystal structures have been determined for the inactive receptors as well as for the G proteins that they bind. PDB entry 3SN6 is the first structure of the full complex of the Beta 2 Adrenergic Receptor bound to Gs in their active state, and it provides the first high-resolution insight into the mechanism of signal transduction across the plasma membrane by a GPCR. | Since these receptors have seven transmembrane helices as well as inner and outer cell regions, they are very difficult to purify and crystalize. Some crystal structures have been determined for the inactive receptors as well as for the G proteins that they bind. PDB entry 3SN6 is the first structure of the full complex of the Beta 2 Adrenergic Receptor bound to Gs in their active state, and it provides the first high-resolution insight into the mechanism of signal transduction across the plasma membrane by a GPCR. | ||
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== G-Protein-GPCR Intercations == | == G-Protein-GPCR Intercations == | ||
The α5-helix of Gαs docks into a cavity formed on the intracellular side of the receptor by the opening of transmembrane helices 5 and 6. Within the transmembrane core, the interactions are primarily non-polar - <scene name='70/701430/Receptor_g_protein_interaction/4'> | The α5-helix of Gαs docks into a cavity formed on the intracellular side of the receptor by the opening of transmembrane helices 5 and 6. Within the transmembrane core, the interactions are primarily non-polar - an exception involves <scene name='70/701430/Receptor_g_protein_interaction/4'>packing</scene> of Tyr 391 of the α5-helix against Arg 131 of the conserved DRY sequence in TM3. Arg 131 also packs against Tyr 326 of the conserved NPxxY sequence in TM7. As the α5-helix exits the receptor it forms a network of polar interactions with TM5 and TM3. Receptor residues Thr 68 and Asp 130 interact with the ICL2 helix of the β2AR via Tyr 141, positioning the helix so that Phe 139 of the receptor <scene name='70/701430/Receptor_gprotein_interaction2/1'>docks into</scene> a hydrophobic pocket on the G protein surface, thereby structurally linking receptor–G protein interactions with the highly conserved DRY motif of the β2AR. | ||
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