Beta2 adrenergic receptor-Gs protein complex: Difference between revisions
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<StructureSection load='3SN6' size='340' side='right' caption='[[3SN6]], [[Resolution|resolution]] 3.20Å' scene=''> | <StructureSection load='3SN6' size='340' side='right' caption='[[3SN6]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
==Introduction== | ==Introduction== | ||
[[G protein-coupled receptors]] (GPCRs) are a large family of protein receptors which have seven-transmembrane helices and are found over a large array | [[G protein-coupled receptors]] (GPCRs) are a large family of protein receptors, which have seven-transmembrane helices and are found over a large array of eukaryotic cells. These receptors take a major part in a multitude of signal transduction pathways, including amongst others responses to hormones and neurotransmitters, sensing light, taste and smell, and many more. These receptors are also involved in many different types of diseases and are the target of almost 50% of current medical drugs. | ||
The [[Beta-2 Adrenergic Receptors]] are a type of | The [[Beta-2 Adrenergic Receptors]] are a type of GPCR that are activated by catecholamine hormone ligands such as adrenaline (epinephrine). These receptors are responsible for many of the adrenaline related (“fight-or-flight”) responses and functions, and are used as a common model system for the GPCR family. | ||
GPCRs bind their ligand and [[Group:SMART:A Physical Model of the β2-Adrenergic Receptor|overcome a conformational change]] | 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 belong to the larger group of enzymes called GTPases <ref>https://en.wikipedia.org/wiki/GTPase</ref>. | |||
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. | ||
== Complex structure == | == Complex structure == | ||
The overall structure shows the <scene name='70/701430/Receptor/1'>β2AR receptor</scene> (dark blue) bound to an agonist (in spheres) along with a <scene name='70/701430/Lysozyme/1'>T4</scene> [https://en.wikipedia.org/wiki/Lysozyme lysozyme] fused to its amino terminus in order to facilitate crystallization. The receptor interacts with <scene name='70/701430/Galpha/1'>Gαs</scene> (light blue). Gαs together with <scene name='70/701430/Gbeta/1'>Gβ</scene> (light green) and <scene name='70/701430/Ggamma/1'>Gγ</scene> (gold) constitute the heterotrimeric G protein Gs. A Gs-binding [https://en.wikipedia.org/wiki/Single-domain_antibody nanobody] <scene name='70/701430/Nanobody/1'>(in pink)</scene> which also facilitates crystallization binds the G protein between the | The overall structure shows the <scene name='70/701430/Receptor/1'>β2AR receptor</scene> (dark blue) bound to an agonist (in spheres) along with a <scene name='70/701430/Lysozyme/1'>T4</scene> [https://en.wikipedia.org/wiki/Lysozyme lysozyme] fused to its amino terminus in order to facilitate crystallization. The receptor interacts with <scene name='70/701430/Galpha/1'>Gαs</scene> (light blue). Gαs together with <scene name='70/701430/Gbeta/1'>Gβ</scene> (light green) and <scene name='70/701430/Ggamma/1'>Gγ</scene> (gold) constitute the heterotrimeric G protein Gs. A Gs-binding [https://en.wikipedia.org/wiki/Single-domain_antibody nanobody] <scene name='70/701430/Nanobody/1'>(in pink)</scene>, which also facilitates crystallization, binds the G protein between the α and β subunits. | ||
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== G-Protein-GPCR Intercations == | == G-Protein-GPCR Intercations == | ||