Figure 1: LPA receptor (blue) bound to the cell membrane. The binding pocket is highlighted in red. The added bRIL protein is highlighted in orange.
Lysophosphatidic Acid
Figure 2: Chemical Structure of LPA (monoacyl-sn-glycero-3-phosphate)
Overall Structure
SHOC2
PP1C
MRAS
Key Ligand Interactions
Figure 3: Electrostatic illustration of the amphipathic binding pocket of the LPA1 receptor. This binding pocket was revealed by cutting away the exterior or the protein. This binding pocket, located in the interior of the protein, has both polar and nonpolar regions. The blue and red coloration highlight the positively and negatively charged regions, respectively, and the white color shows the nonpolar region of the binding pocket.
SHOC2 and PP1C
SHOC2 and MRAS
PP1C and MRAS
Signaling Pathway
Figure 1:Comparison of Delta-opioid receptor to human free-fatty acid receptor (hGPR40) both of which are G-protein coupled receptors. The binding pocket of the delta-opioid receptor is solvent exposed allowing ligands to enter directly from the extracellular space while the binding pocket of hGPR40 is covered by the extracellular loop 2 (ECL2) preventing entry from the extracellular space (ECL2 represented in cyan). The Delta-opioid displays the canonical binding site typical of most GPCRs while ligands of hGPR40 bind to a noncanonical pocket represented in pink.
Disease Relevance
Cancer
RASopathies
Future Studies
3D structures of lysophosphatidic acid receptor
4z34, 4z35, 4z36 - hLPA1 + antagonist - human 2lq4 – hLPA1 second extracellular loop – NMR 4p0c – hLPA2/NHERF2 5xsz – LPA6A (mutant) – zebra fish
