Short Report by Brennica Marlow: Allosteric modulation of the Oxytocin receptor by cholesterol. (Jan.-April 2023)

/ March 20, 2023/ News, Research

A previous postdoctoral research, in the Meiler Lab with 8 years of experience researching cholesterol interactions with membrane proteins.

Research Summary
Cholesterol is one of the most studied lipids as it relates to protein-lipid interactions. Cholesterol plays multiple biological roles in bile acid synthesis, steroidogenesis, and membrane dynamic function. Increasingly, evidence has shown that cholesterol also acts as a direct binder to IMPs, including G-protein coupled receptors (GPCRs). GPCRs are a protein superfamily containing seven transmembrane helices that are responsible for a wide variety of signaling responses. The seven helices form a hydrophobic pocket accessible from the extracellular side, forming the orthosteric pocket for endogenous ligands to bind to. The binding of these ligands to the orthosteric pocket has been shown to be allosterically modulated by cholesterol binding. This is especially important to note because GPCRs make up more than 30% of the currently marketed drugs, thus representing a very important pharmacological target. It is unclear how cholesterol allosterically modifies the affinity of the orthosteric ligand. So here, we map the allosteric network that causes this phenomenon using a combination of molecular docking and MD simulations.

Cultural Experience
During my time in Germany, I visited countries like Spain and Italy, but my most exciting excursion was to Dresden. Dresden offered a rich cultural experience with historical architecture and art collections. A cultural highlight was visiting the Frauenkirche, which was a symbol of the city’s resilience and reconstruction. Along those lines, I toured the historic city center with cobblestone streets and squares like Neumarkt, exploring the local shops and restaurants. Additionally, a short train ride away I hiked the Bastei. Visiting the Bastei offered a breathtaking experience with a bridge that provided panoramic views of the frozen Elbe River. Overall, my visit to Dresden and the Bastei constituted a cultural immersion into a rich history, architecture, and nature.