Bile acid binding protein (BABP) (BABP)

Bile acid binding proteins (BABPs) are low molecular weight proteins (~14 kDa) that belong to the intracellular lipid binding protein (iLBP) family. They are characterized by approximately 125 amino acid residues folded into ten antiparallel beta-strands that form a clamshell-like structure, capped by a pair of alpha-helices, which creates an internal cavity for ligand binding[1][2]. BABPs are primarily found in the liver (L-BABP) and intestine (I-BABP), where they facilitate the intracellular transport of bile acids. These proteins exhibit unique binding properties including positive binding cooperativity and site-selectivity, which appear to be tailored to the local bile salt pool in different tissues and organisms[1]. The main function of BABPs is to bind and shuttle bile acids across the cytosol, facilitating their intracellular solubilization and trafficking between membranes[2]. This is crucial for the enterohepatic circulation of bile acids, which are physiological detergents that facilitate absorption, transport, and distribution of lipid-soluble vitamins and dietary fats[3]. Structurally, BABPs can bind one or two bile acid molecules in their internal cavity, and some BABPs have been shown to bind additional ligands on their molecular surface[2]. The binding mechanism involves significant conformational changes and backbone flexibility, particularly in regions located at the protein's open end, which facilitates bile salt exchange[3]. Disorders in bile acid transport and metabolism have been linked to various disease states, including atherosclerosis, type-II diabetes, and cancer[1]. Understanding the structural and dynamic determinants of bile salt binding at the atomic level provides insights for the design and development of drug candidates targeting the transcellular traffic of bile salts in enterocytes and hepatocytes[1].

Other names

Liver bile acid-binding protein (L-BABP)Liver basic fatty acid-binding protein (Lb-FABP)Intestinal bile acid-binding protein (I-BABP)14-kDa bile acid-binding protein (14-kDa I-BABP)Cytosolic bile acid binding protein

Binding and shuttling bile acids across the cytosol; Positive binding cooperativity; Site-selectivity for different bile salts; Conformational selection mechanism