More cholesterol binds to the active form of the glucagon-like peptide-1 receptor

Cholesterol shows increased interactions with the active conformational states of the glucagon-like peptide-1 receptor (GLP-1R).

• Cholesterol hotspots differ across the inactive, partially active, GLP-1-bound active, and exenatide-bound active states of GLP-1R.
• The active states of GLP-1R exhibit a higher enrichment of cholesterol compared to the inactive state.
• More favorable interaction energetics and longer residence times of cholesterol were observed in the active state of GLP-1R, although these findings are less pronounced than previously reported.
• Differences in cholesterol interactions were noted between the GLP-1-bound and exenatide-bound active states, suggesting ligand-specific effects.
• The study highlights the importance of conformational dynamics in the interaction between cholesterol and GLP-1R.

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