Insights into AT1 receptor activation through AngII binding studies.
This study investigates the binding of angiotensin II (AngII) to the angiotensin II type 1 receptor (AT1R), taking into consideration several known activation elements that have been observed for G-protein-coupled receptors (GPCRs). In order to determine the crucial interactions of AngII upon binding, several MD simulations were implemented using AngII conformations derived from experimental data (NMR ROEs) and in silico flexible docking methodologies. An additional goal was to simulate the induced activation mechanism and examine the already known structural rearrangements of GPCRs upon activation. Performing MD simulations to the AT1R - AngII - lipids complex, a series of dynamic changes in the topology of AngII and the intracellular part of the receptor were observed. Overall, the present study proposes a complete binding profile of AngII to the AT1R, as well as the key transitional elements of the receptor and the agonist peptide upon activation through NMR and in silico studies.
Laboratori de Medicina Computacional, Unitat de Bioestadıstica, Facultat de Medicina, Universitat Autonoma de Barcelona , E-08193, Bellaterra, Barcelona, Spain.
Minos-Timotheos
MT
Matsoukas
Constantinos
C
Potamitis
Panayiotis
P
Plotas
Maria-Eleni
ME
Androutsou
George
G
Agelis
John
J
Matsoukas
Panagiotis
P
Zoumpoulakis
D019342:Acetic Acid / Q000737:chemistry; D000804:Angiotensin II / Q000737:chemistry*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry*; D001665:Binding Sites; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry*; D019718:Receptors, CXCR4 / Q000737:chemistry; D040681:Structural Homology, Protein; D013816:Thermodynamics; D014269:Trifluoroacetic Acid / Q000737:chemistry
D047228:Angiotensin II Type 1 Receptor Blockers; C527276:CXCR4 protein, human; D008024:Ligands; D044140:Receptor, Angiotensin, Type 1; D019718:Receptors, CXCR4; D000804:Angiotensin II; D014269:Trifluoroacetic Acid; D019342:Acetic Acid; D004121:Dimethyl Sulfoxide