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

Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Apr;1863(4):458-466. doi: 10.1016/j.bbalip.2018.01.010.

Abstract

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.

Keywords: Fatty acid; Lipocalin, TTR, Transthyretin, formerly called prealbumin; RBP4, Plasma retinol-binding protein; X-ray structure.

MeSH terms

  • Amniotic Fluid / metabolism
  • Crystallography, X-Ray
  • Fatty Acid-Binding Proteins / blood*
  • Fluorescence
  • Humans
  • Ligands
  • Mass Spectrometry
  • Models, Molecular
  • Retinol-Binding Proteins, Plasma / chemistry
  • Retinol-Binding Proteins, Plasma / isolation & purification
  • Retinol-Binding Proteins, Plasma / metabolism*
  • Retinol-Binding Proteins, Plasma / urine
  • Static Electricity
  • Vitamin A / metabolism

Substances

  • Fatty Acid-Binding Proteins
  • Ligands
  • RBP4 protein, human
  • Retinol-Binding Proteins, Plasma
  • Vitamin A