Structural Stringency of Cholesterol for Membrane Protein Function Utilizing Stereoisomers as Novel Tools: A Review

Cholesterol is an important lipid in the context of membrane protein function. The function of a number of membrane proteins, including G protein-coupled receptors (GPCRs) and ion channels, has been shown to be dependent on membrane cholesterol. However, the molecular mechanism underlying such regulation is still being explored. In some cases, specific interaction between cholesterol and the protein has been implicated. In other cases, the effect of cholesterol on the membrane properties has been attributed for the regulation of protein function. In this article, we have provided an overview of experimental approaches that are useful for determining the degree of structural stringency of cholesterol for membrane protein function. In the process, we have highlighted the role of immediate precursors in cholesterol biosynthetic pathway in the function of membrane proteins. Special emphasis has been given to the application of stereoisomers of cholesterol in deciphering the structural stringency required for regulation of membrane protein function. A comprehensive examination of these processes would help in understanding the molecular basis of cholesterol regulation of membrane proteins in subtle details.