Cholesterol-Dependent Cellular Processes and Peptides Containing Cholesterol-Binding Motifs: Possible Implications for Medicine

Abstract

The animal cell is a unique system in which the functioning of its constituent molecules is interdependent and coordinated, and the violation of this coordination is fatal for the cell. One example of this coordination and mutual regulation is the functioning of membrane proteins, whose activity depends on their interaction with membrane lipids. This review reminds us of the crucial importance of the lipid component of cell membranes for normal cell function, and in particular looks at the role of the "cholesterol" component. Given a given genome and a corresponding set of proteins, this lipid component provides a wide range of regulation of cellular functions. The review exemplifies cholesterol-dependent membrane proteins and cellular processes and considers their role in microbial infections and some other pathologies. The concept of cholesterol-recognizing/interacting amino acid consensus (CRAC) motifs in proteins as a possible mechanism of these protein–lipid interactions is discussed. Examples of the use of peptides containing such motifs to modulate cholesterol-dependent processes are presented. In summary, consideration of the cholesterol component in disease pathogenesis and understanding the mechanisms of cholesterol–protein interactions represent a significant resource for the development of drugs that affect the protein–lipid interface. Such drugs may include cholesterol-binding peptides that target specific cholesterol-dependent proteins.