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 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'. Their activity is thus regulated by factors that control their ability to bind to GTP and hydrolyze it to GDP | 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'. Their activity is thus regulated by factors that control their ability to bind to GTP and hydrolyze it to GDP. | ||
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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[[Image:ImgSmall1.jpg|500px|G protein cycle for the β2AR–Gs complex. Reprinted by permission from Macmillan Publishers Ltd on behalf of Cancer Research UK: Nature 477, 549–555, copyright 2011]] | [[Image:ImgSmall1.jpg|500px|G protein cycle for the β2AR–Gs complex. Reprinted by permission from Macmillan Publishers Ltd on behalf of Cancer Research UK: Nature 477, 549–555, copyright 2011]] | ||
The figure shows the G Protein cycle <ref>doi:10.1038/nature10361</ref> - an extracellular agonist binding to the β2AR leads to <scene name='70/701430/Receptor_morphing_animation/2'>conformational rearrangements</scene> of the cytoplasmic ends of transmembrane segments that enable the Gs heterotrimer to bind the receptor. GDP is released from the α subunit upon formation of β2AR–Gs complex. The GTP binds to the nucleotide-free α subunit resulting in dissociation of the α and βγ subunits from the receptor. The subunits regulate their respective effector proteins adenylyl cyclase (AC) and Ca2+ channels. The Gs heterotrimer reassembles from α and βγ subunits following hydrolysis of GTP to GDP in the α subunit. | The figure shows the G Protein cycle<ref>doi:10.1038/nature10361</ref> - an extracellular agonist binding to the β2AR leads to <scene name='70/701430/Receptor_morphing_animation/2'>conformational rearrangements</scene> of the cytoplasmic ends of transmembrane segments that enable the Gs heterotrimer to bind the receptor. GDP is released from the α subunit upon formation of β2AR–Gs complex. The GTP binds to the nucleotide-free α subunit resulting in dissociation of the α and βγ subunits from the receptor. The subunits regulate their respective effector proteins adenylyl cyclase (AC) and Ca2+ channels. The Gs heterotrimer reassembles from α and βγ subunits following hydrolysis of GTP to GDP in the α subunit. | ||
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