Human plasma retinol-binding protein (RBP4) is also a fatty acid-binding protein. 2018

Massimiliano Perduca, and Stefania Nicolis, and Barbara Mannucci, and Monica Galliano, and Hugo L Monaco
Biocrystallography Laboratory, Department of Biotechnology, University of Verona, Ca Vignal 1, strada Le Grazie 15, 37134 Verona, Italy.

RBP4 (plasma retinol-binding protein) is the 21 kDa transporter of all-trans retinol that circulates in plasma as a moderately tight 1:1 molar complex of the vitamin with the protein. RBP4 is primarily synthesized in the liver but is also produced by adipose tissue and circulates bound to a larger protein, transthyretin, TTR, that serves to increase its molecular mass and thus avoid its elimination by glomerular filtration. This paper reports the high resolution three-dimensional structures of human RBP4 naturally lacking bound retinol purified from plasma, urine and amniotic fluid. In all these crystals we found a fatty acid molecule bound in the hydrophobic ligand-binding site, a result confirmed by mass spectrometry measurements. In addition we also report the 1.5 Å resolution structures of human holo-RBP4 and of the protein saturated with palmitic and lauric acid and discuss the interaction of the fatty acids and retinol with the protein.

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D005453 Fluorescence The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000653 Amniotic Fluid A clear, yellowish liquid that envelopes the FETUS inside the sac of AMNION. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (AMNIOCENTESIS). Amniotic Fluid Index,Amniotic Fluid Indices,Amniotic Fluids,Fluid Index, Amniotic,Fluid Indices, Amniotic,Fluid, Amniotic,Fluids, Amniotic,Index, Amniotic Fluid,Indices, Amniotic Fluid
D013058 Mass Spectrometry An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers. Mass Spectroscopy,Spectrometry, Mass,Spectroscopy, Mass,Spectrum Analysis, Mass,Analysis, Mass Spectrum,Mass Spectrum Analysis,Analyses, Mass Spectrum,Mass Spectrum Analyses,Spectrum Analyses, Mass
D014801 Vitamin A Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of CAROTENOIDS found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Retinol,11-cis-Retinol,3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ol, (all-E)-Isomer,All-Trans-Retinol,Aquasol A,Vitamin A1,All Trans Retinol
D050556 Fatty Acid-Binding Proteins Intracellular proteins that reversibly bind hydrophobic ligands including: saturated and unsaturated FATTY ACIDS; EICOSANOIDS; and RETINOIDS. They are considered a highly conserved and ubiquitously expressed family of proteins that may play a role in the metabolism of LIPIDS. Fatty Acid-Binding Protein,Adipocyte Lipid Binding Protein,Adipocyte-Specific Fatty Acid-Binding Protein,Brain-Type Fatty Acid-Binding Protein,Cytosolic Lipid-Binding Proteins,Fatty Acid-Binding Protein, Cardiac Myocyte,Fatty Acid-Binding Protein, Myocardial,Fatty Acid-Binding Proteins, Adipocyte-Specific,Fatty Acid-Binding Proteins, Brain-Specific,Fatty Acid-Binding Proteins, Cytosolic-Specific,Fatty Acid-Binding Proteins, Intestinal-Specific,Fatty Acid-Binding Proteins, Liver-Specific,Fatty Acid-Binding Proteins, Myocardial-Specific,Fatty Acid-Binding Proteins, Plasma-Membrane Specific,Intestinal Fatty Acid-Binding Protein,Liver Fatty Acid-Binding Protein,Myocardial Fatty Acid-Binding Protein,Plasma Membrane Fatty Acid-Binding Protein,Acid-Binding Protein, Fatty,Adipocyte Specific Fatty Acid Binding Protein,Brain Type Fatty Acid Binding Protein,Cytosolic Lipid Binding Proteins,Fatty Acid Binding Protein,Fatty Acid Binding Protein, Cardiac Myocyte,Fatty Acid Binding Protein, Myocardial,Fatty Acid Binding Proteins,Fatty Acid Binding Proteins, Adipocyte Specific,Fatty Acid Binding Proteins, Brain Specific,Fatty Acid Binding Proteins, Cytosolic Specific,Fatty Acid Binding Proteins, Intestinal Specific,Fatty Acid Binding Proteins, Liver Specific,Fatty Acid Binding Proteins, Myocardial Specific,Fatty Acid Binding Proteins, Plasma Membrane Specific,Intestinal Fatty Acid Binding Protein,Lipid-Binding Proteins, Cytosolic,Liver Fatty Acid Binding Protein,Myocardial Fatty Acid Binding Protein,Plasma Membrane Fatty Acid Binding Protein,Protein, Fatty Acid-Binding
D054839 Retinol-Binding Proteins, Plasma Retinol binding proteins that circulate in the PLASMA. They are members of the lipocalin family of proteins and play a role in the transport of RETINOL from the LIVER to the peripheral tissues. The proteins are usually found in association with TRANSTHYRETIN. Plasma Retinol-Binding Proteins,Plasma Retinol Binding Proteins,Retinol Binding Proteins, Plasma
D055672 Static Electricity The accumulation of an electric charge on a object Electrostatic,Electrostatics,Static Charge,Charge, Static,Charges, Static,Electricity, Static,Static Charges

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