Membrane cholesterol stabilizes the human serotonin(1A) receptor

A number of recently solved crystal structures of G-protein coupled receptors reveal the presence of closely associated cholesterol molecules in the receptor structure. We have previously shown the requirement of membrane cholesterol in the organization, dynamics and function of the serotonin(1A) receptor, a representative G-protein coupled receptor. In this work, we explored the role of membrane cholesterol in the stability of the human serotonin(1A) receptor. Analysis of sensitivity of the receptor to thermal deactivation, pH, and proteolytic digestion in control, cholesterol-depleted and cholesterol-enriched membranes comprehensively demonstrate that membrane cholesterol stabilizes the serotonin(1A) receptor. We conclude that these results could have potential implications in future efforts toward crystallizing the receptor.