User:Daniel Schemenauer/Sandbox 1: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 11: | Line 11: | ||
A <scene name='72/726404/Scene_6/3'>Disulfide Bond </scene> between Cysteine 644 of TM3 and Cysteine 733 of ECL2 is critical at anchoring ECL2 and is highly conserved across Class C GPCR’s<ref name="Primary">PMID: 25042998 </ref>. The ECL2 position combined with the helical bundle of the trans-membrane domain creates a <scene name='72/726409/Electrogradient2/3'>Binding Cap</scene> that restricts entrance to the allosteric binding site within the seven trans-membrane α-helices. This restricted entrance has no effect on the natural ligand, glutamate, as it binds to the extracellular domain, but this entrance dictates potential drug targets that act through allosteric modulation<ref name="Primary">PMID: 25042998 </ref>. | A <scene name='72/726404/Scene_6/3'>Disulfide Bond </scene> between Cysteine 644 of TM3 and Cysteine 733 of ECL2 is critical at anchoring ECL2 and is highly conserved across Class C GPCR’s<ref name="Primary">PMID: 25042998 </ref>. The ECL2 position combined with the helical bundle of the trans-membrane domain creates a <scene name='72/726409/Electrogradient2/3'>Binding Cap</scene> that restricts entrance to the allosteric binding site within the seven trans-membrane α-helices. This restricted entrance has no effect on the natural ligand, glutamate, as it binds to the extracellular domain, but this entrance dictates potential drug targets that act through allosteric modulation<ref name="Primary">PMID: 25042998 </ref>. | ||
===Comparison with Class A and B GPCRs=== | ===Comparison with Class A and B GPCRs=== | ||
The structure of the trans-membrane domain of mGlu<sub>5</sub> was compared to rhodopsin, a class A GPCR, and CRF<sub>1</sub>R, a class B GPCR. The superimposition of all three structures demonstrated the greatest divergence occurred across the top half of the trans-membrane bundle, attributing to the different extracellular domains that accompany each GPCR class. Furthermore, mGlu<sub>5</sub> TM7 is shifted inwards | The structure of the trans-membrane domain of mGlu<sub>5</sub> was compared to rhodopsin, a class A GPCR, and CRF<sub>1</sub>R, a class B GPCR. The superimposition of all three structures demonstrated the greatest divergence occurred across the top half of the trans-membrane bundle, attributing to the different extracellular domains that accompany each GPCR class. Furthermore, mGlu<sub>5</sub> TM7 is shifted inwards 5 Å compared to the class A GPCR, and TM5 is shifted inwards 6 Å compared to both GPCRs, thus narrowing the allosteric binding entrance <ref name="Primary">PMID: 25042998 </ref>. | ||
== Clinical Relevance == | == Clinical Relevance == | ||
===Role in Diseases=== | ===Role in Diseases=== | ||
