The angiotensin II type 1 (AT1) receptor is the member of GPCR A family which biological functions are linked with hypertension and cognitive heart failure. AT1 receptor is one of the very few receptor which can be activated by the natural agonist as well by membrane tension. It was known for a long time that AT1 receptor can be activated independent of ligand. However the lack of high resolution structure has been the downside to gain the different structural insight of its active states. The different activation of the receptor is related with the interaction different kind of effector like G-proteins and beta-arrestin. We have characterized the activation of AT1 receptor under different lipid bilayer with varying acyl chain length as well as the membrane tension. The microseconds long molecular dynamics simulations showed the stability of the receptor is membrane thickness dependent and sensitive to membrane tension. Furthermore, we have computed the free energy surface for ligand induced and membrane induced activation. The free energy surface showed that the different activation results the distinct active structure. Our modeling approach predicts the structural insights of ligand-induced and membrane-induced activation and how they are compared.

Activation of angiotensin II type 1 (AT1) receptor independent of agonist

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