retinoidbinding

Retinoid binding refers to the specific interaction of retinoids—lipophilic derivatives of vitamin A such as retinol, retinal, and retinoic acid—with binding proteins and other macromolecules. These interactions control solubility, transport, storage, metabolism, and signaling of retinoids in vertebrates, and influence tissue distribution and receptor activation.

In blood, the principal carrier of retinol is retinol-binding protein 4 (RBP4). Retinol circulates bound to RBP4 and, to prevent renal loss, forms a complex with transthyretin. Retinoids can also associate with albumin and lipoproteins in plasma, providing auxiliary distribution routes. Cellular uptake often involves receptor-mediated mechanisms (for example, uptake of RBP–retinol via STRA6) or endocytosis of albumin-bound retinol, depending on tissue context.

Within cells, retinoid binding proteins ensure proper trafficking and metabolism. Cellular retinol-binding protein 1 (CRBP1) binds retinol and retinal, guiding substrates to enzymes such as LRAT and retinol dehydrogenases. CRBP2 functions similarly in the intestine. Cellular retinoic acid-binding proteins CRABP I and CRABP II bind all-trans-retinoic acid and regulate its availability to metabolic enzymes and to nuclear receptors RAR and RXR. CRABP2 is often associated with promoting signaling to these receptors, whereas CRABP1 can modulate cytosolic RA pools. Other proteins, such as FABP5, can shuttle RA to alternative signaling pathways.

The retinoid-binding network regulates catabolism by CYP26 enzymes and protects cells from retinoid excess and oxidative damage. Disruption of binding partners or transport pathways can lead to deficiency or toxicity and affects the pharmacokinetics of retinoid therapies used in medicine. Research uses structural biology and binding assays to map affinities, pockets, and dynamics underpinning retinoid biology.