Sandbox Reserved 1172

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=== Sphingosine 1-Phosphate Receptor ===
=== Sphingosine 1-Phosphate Receptor ===
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LPA1 belongs to the EDG family of lysophospholipid receptors. This family also includes the sphingosine 1-phosphate receptor 1 (S1P1), which has many structural similarities to LPA1. In fact, the transmembrane regions share a sequence identity of 41%. A defining difference between these two receptors their mode of ligand access to the binding site. Where as the hydrophobic S1P ligand enters S1P1 via the membrane, LPA1 has an extracellular opening that allows LPA access from the extracellular space. Structural evidence for this altered ligand pathway include global changes in the positioning of the extracellular loops (ECL) and transmembrane helices (TM). Specifically, this includes slight divergence of <scene name='72/721543/Tmvii_and_tmi/1'>TMI</scene>, which is positioned 3 angstroms closer to TMVII compared to S1P1, and a repositioning of <scene name='72/721543/Ecl_regions/1'>ECL3</scene>, resulting in a divergence of 8 angstroms form S1P1. This narrowing of the gap between TMI and TMVII blocks membrane ligand access, while the greater distance between ECL3 and the other extracellular loops promotes extracellular access. Additionally, ECL0 is helical in S1P1, but lacks secondary structure in LPA1. This increased flexibility that results further promotes favorable access from the extracellular space.
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<scene name='72/721543/Tmvii_and_tmi/1'>TextToBeDisplayed</scene>
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<scene name='72/721543/Tmvii_and_tmi/1'>TMI</scene>
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<scene name='72/721543/Ecl_regions/1'>TextToBeDisplayed</scene>
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<scene name='72/721543/Ecl_regions/1'>ECL3</scene>
=== Endocannabinoid Receptor 1 ===
=== Endocannabinoid Receptor 1 ===

Revision as of 04:37, 29 March 2016

This Sandbox is Reserved from Jan 11 through August 12, 2016 for use in the course CH462 Central Metabolism taught by R. Jeremy Johnson at the Butler University, Indianapolis, USA. This reservation includes Sandbox Reserved 1160 through Sandbox Reserved 1184.
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Lysophosphatidic Acid Receptor 1

Cartoon representation of the LPA1 protein and its antagonist, ON7. (PDB code 4Z34)

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References

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