1b:I[76749,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 1c:I[3486,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 1d:I[41892,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 1e:I[17707,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 1f:I[66528,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 20:I[63176,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 21:I[87099,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 22:I[26200,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"Group"] 23:I[23365,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 24:T4cc,Cholesterol is a major component of the cell membrane and commonly regulates membrane protein function. Here, we investigate how cholesterol modulates the conformational equilibria and signaling of the adenosine A_2A receptor (A_2AR) in reconstituted phospholipid nanodiscs. This model system conveniently excludes possible effects arising from cholesterol-induced phase separation or receptor oligomerization and focuses on the question of allostery. GTP hydrolysis assays show that cholesterol weakly enhances the basal signaling of A_2AR while decreasing the agonist EC₅₀. Fluorine nuclear magnetic resonance (¹⁹F NMR) spectroscopy shows that this enhancement arises from an increase in the receptor's active state population and a G-protein-bound precoupled state. ¹⁹F NMR of fluorinated cholesterol analogs reveals transient interactions with A_2AR, indicating a lack of high-affinity binding or direct allosteric modulation. The combined results suggest that the observed allosteric effects are largely indirect and originate from cholesterol-mediated changes in membrane properties, as

Omar Almurad

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