Structural aspects of binding and transport proteins : By Barnali Neel Chaudhuri

Abstract: Binding and transport proteins are essential for the transport of nutrients, vitamins, hormones, pheromones, etc. to their target destinations. Lipid-binding proteins typically contain an internal cavity where the hydrophobic/amphipathic ligands bind. Transport proteins with binding clefts for water-soluble sugars have different architectures. Access to the cavity or the cleft sometimes requires conformational changes in the protein. This thesis presents the structures of three classes of bindingproteins.The cellular retinoid binding proteins sequester the amphipathic retinoids (vitamin A analogues) within the cytoplasm. The anti-carcinogenic properties of some synthetic retinoids make them interesting as potential drugs. The structures of cellular retinoic acid binding proteins were determined in complex with three different retinoids. In addition, the structure of a ligand-free mutant of cellular retinol binding protein was determined in order to study ligand entry into the cavity.The structure of α2U-globulin, an extra-cellular lipid-binding protein, was obtained in complex with a toxin, d-limonene 1,2-epoxide. The nature of the hydrophobic ligand-binding cavity is described in the context of a male rat specific nephropathy induced by this toxin.Allose binding protein from Escherichia coli belongs to the family of periplasmic binding proteins. Structures of this protein in the closed, allose-bound and the open, ligand-free form were determined to study the binding cleft and hinge bending. The protein consists of two Rossmann fold domains joined by a flexible, three-stranded hinge region. The binding cleft is formed at the domain interface in the closed form. Integral water molecules play an important structural role in the hinge.