Activation-Induced Reorganization of Energy Transport Networks in the β2 Adrenergic Receptor
| Autor: | Humanath Poudel, David M. Leitner |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Molecular switch
Agonist 010304 chemical physics Chemistry medicine.drug_class Allosteric regulation 010402 general chemistry 01 natural sciences 0104 chemical sciences Surfaces Coatings and Films GTP-binding protein regulators 0103 physical sciences Materials Chemistry Biophysics medicine Physical and Theoretical Chemistry Signal transduction Binding site Receptor G protein-coupled receptor |
| Zdroj: | The Journal of Physical Chemistry B. 125:6522-6531 |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/acs.jpcb.1c03412 |
| Popis: | We compute energy exchange networks (EENs) through the β2 adrenergic receptor (β2AR), a G-protein coupled receptor (GPCR), in inactive and active states, based on the results of molecular dynamics simulations of this membrane bound protein. We introduce a new definition for the reorganization of EENs upon activation that depends on the relative change in rates of energy transfer across noncovalent contacts throughout the protein. On the basis of the reorganized network that we obtain for β2AR upon activation, we identify a branched pathway between the agonist binding site and the cytoplasmic region, where a G-protein binds to the receptor when activated. The pathway includes all of the motifs containing molecular switches previously identified as contributing to the allosteric transition of β2AR upon agonist binding. EENs and their reorganization upon activation are compared with structure-based contact networks computed for the inactive and active states of β2AR. |
| Databáze: | OpenAIRE |
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