Sandbox Reserved 1160
From Proteopedia
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== Discovery == | == Discovery == | ||
| - | The mGlu family of receptors was the first of the Class C [[GPCR]] to be extensively studied<ref name="Wu" />. The first regions of the protein crystallized and studied were the Venus Fly Trap domain and the cystiene -rich domain on the extracellular region of the receptor<ref name="Dore" />.The Venus Flytrap domain is a large extracellular domain that will selectively bind to glutamate<ref name="Wu" />. The CRD is a somewhat smaller domain composed of many B sheets and cystiene residues <ref name="Wu" />. The CRD acts as a signal mediator between the Venus Flytrap domain and the TMD of mGlu5, by linking to each domain with disulfide bonds<ref name="Wu" />. The hydrophobic nature and flexibility of the transmembrane domain made it difficult to crystallize. Recently, the human metabotropic glutamate receptor 5 transmembrane domain (TMD) was crystallized and a structure elucidated<ref name="Dore" />. Several modifications made to the TMD for successful crystallization. The protein was thermostabilized and flexible domains were removed<ref name="Dore" />. In total residue 2-568 and residues 837-1153 were excised from the structure. Also, a T4 -<scene name='72/721531/Protien_lys/1'>Lysozyme</scene> was inserted into | + | The mGlu family of receptors was the first of the Class C [[GPCR]] to be extensively studied<ref name="Wu" />. The first regions of the protein crystallized and studied were the Venus Fly Trap domain and the cystiene -rich domain on the extracellular region of the receptor<ref name="Dore" />.The Venus Flytrap domain is a large extracellular domain that will selectively bind to glutamate<ref name="Wu" />. The CRD is a somewhat smaller domain composed of many B sheets and cystiene residues <ref name="Wu" />. The CRD acts as a signal mediator between the Venus Flytrap domain and the TMD of mGlu5, by linking to each domain with disulfide bonds<ref name="Wu" />. The hydrophobic nature and flexibility of the transmembrane domain made it difficult to crystallize. Recently, the human metabotropic glutamate receptor 5 transmembrane domain (TMD) was crystallized and a structure elucidated<ref name="Dore" />. Several modifications made to the TMD for successful crystallization. The protein was thermostabilized and flexible domains were removed<ref name="Dore" />. In total residue 2-568 and residues 837-1153 were excised from the structure. Also, a T4 -<scene name='72/721531/Protien_lys/1'>Lysozyme</scene> was inserted into Intracellular loop 2 to add stability<ref name="Dore" />. |
== Structure== | == Structure== | ||
[[Image:STR.png|200 px|left|thumb|'''Figure 1''': Overall Structure of the mGlu5 TMD. The polar heads on the Oliec acids orient the image with the top oriented extracellularly, the middle portion inserted into the membrane, and the lower portion oriented intracellularly. The white exterior represents the surface of the protien, and the multicolored lones interior to the surface represent the backbones 7 transmembrane alpha helices. ]] | [[Image:STR.png|200 px|left|thumb|'''Figure 1''': Overall Structure of the mGlu5 TMD. The polar heads on the Oliec acids orient the image with the top oriented extracellularly, the middle portion inserted into the membrane, and the lower portion oriented intracellularly. The white exterior represents the surface of the protien, and the multicolored lones interior to the surface represent the backbones 7 transmembrane alpha helices. ]] | ||
=== Overview === | === Overview === | ||
| - | The mGlu5 TMD contains 7 <scene name='72/721531/Protien_7_helices/ | + | The mGlu5 TMD contains 7 <scene name='72/721531/Protien_7_helices/3'> alpha helices</scene> that spans the membrane. The protein was crystallized with Oleic acid and MES. On the superior portion of the protein there are several critical extracellular loops. The binding pocket can be found near the middle of the protein. Inserted into the biding pocket is the negative allosteric modulator [http://www.en.wikipedia.org/wiki/Mavoglurant mavoglurant]. It is important to note that the TMD as illustrated is in an inactive conformation. On the intracellular portion of the protein there exist several ionic locks whose positions will determine the activity of the protein. |
=== Extracellular Domain === | === Extracellular Domain === | ||
These are the <scene name='72/721532/Ecl_trail_1/7'>Extracellular Loops</scene> with extracellular loops (ECLs) 1, 2, and 3 highlighted in purple. Additionally in the ECL domain, a <scene name='72/721532/Ecl_trail_1/6'>disulfide bond</scene> is attached to both Helix 3 and the amino acid chain between Helix 5 and the N terminus. The disulfide bond is highlighted in yellow, and it is conserved in all classes of glutamate receptor 5 transmembrane domains<ref name="Wu" />. | These are the <scene name='72/721532/Ecl_trail_1/7'>Extracellular Loops</scene> with extracellular loops (ECLs) 1, 2, and 3 highlighted in purple. Additionally in the ECL domain, a <scene name='72/721532/Ecl_trail_1/6'>disulfide bond</scene> is attached to both Helix 3 and the amino acid chain between Helix 5 and the N terminus. The disulfide bond is highlighted in yellow, and it is conserved in all classes of glutamate receptor 5 transmembrane domains<ref name="Wu" />. | ||
Revision as of 23:23, 7 April 2016
Human metabotropic glutamate receptor 5 transmembrane domain
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