Cholesterolbinding

Cholesterol binding refers to the association of cholesterol with other molecules, particularly membrane proteins and lipids, through noncovalent forces such as hydrophobic interactions, van der Waals contacts, and, in some cases, electrostatic interactions. Binding can be specific, via defined recognition motifs, or nonspecific, driven by cholesterol's hydrophobic character within the lipid bilayer.

In biological membranes, cholesterol is surrounded by lipids and can form direct contacts with proteins. Some proteins contain cholesterol-binding domains or motifs, including classic cholesterol recognition/interaction consensus sequences (CRAC) and the reverse CARC motif, which facilitate association with cholesterol on cytosolic or extracellular faces. Other interactions are less well defined but still contribute to binding affinity.

Functions of cholesterol binding include shaping membrane order, promoting or stabilizing lipid rafts, and modulating the activity, localization, and trafficking of membrane proteins. Binding can influence receptor clustering, ion channel gating, enzyme activity, and endocytosis, thereby impacting signaling and transport processes.

Notable cholesterol-binding proteins and systems include STARD family members that transfer cholesterol between membranes, NPC1 and NPC2 proteins involved in lysosomal cholesterol trafficking, and caveolin, which participates in cholesterol-rich caveolae. Many receptors and channels display cholesterol-dependent activity, and CRAC/CARC motifs have been implicated in diverse proteins.

Methods to study cholesterol binding include binding assays, fluorescence spectroscopy, surface plasmon resonance, X-ray crystallography, NMR, and computational docking. Understanding cholesterol binding is relevant to physiology and disease, including Niemann-Pick disease type C and disorders related to cholesterol transport and signaling.