Figure 1 | Scientific Reports

Figure 1

From: Lys39-Lysophosphatidate Carbonyl Oxygen Interaction Locks LPA1 N-terminal Cap to the Orthosteric Site and partners Arg124 During Receptor Activation

Figure 1

Classical GPCR activation signature in LPA-type agonist bound LPA1.

(a) Free-energy surface of apo-LPA1. Inset depicts intermediately activated LPA1 (green cartoon) superimposed on the starting LPA1 structure (purple cartoon). R3.50 and L6.33 are shown as stick representation. (b) Distribution of Cα-NPxxY (N7.49-Y7.53) rmsd from inactive and TM3(Cα-R3.50)-TM6 (Cα-L6.33) distance in structures generated within the last 100. (c, i–iv) Dynamic network between cytoplasmic ends of transmembrane helices in VPC32183, AGP18:1, LPA18:1 and LPA20:4 bound LPA1. (d, i–v) Average internal water density flow along LPA1 bound to strong agonists (LPA20:4, LPA18:1 and AGP18:1), weak agonists (LPA 16:0) and an antagonist (VPC32183). (e, i–viii) Free-energy surface representation of LPA1 P7.50 dihedral angle bound to strong and weak agonists and antagonist. Each dot in “b” represents the mean value of three independent simulations, the green arrow depecits the movement of TM6 away from the ionic lock zone.

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