Biocrystallography Laboratory, Department of Biotechnology, University of Verona, Ca Vignal 1, strada Le Grazie 15, 37134 Verona, Italy.
Department of Chemistry, via Torquato Taramelli 12, University of Pavia, 27100 Pavia, Italy.
Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Apr;1863(4):458-466. doi: 10.1016/j.bbalip.2018.01.010.
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.
RBP4（血浆视黄醇结合蛋白）是视黄醇的 21kDa 转运蛋白，在血浆中以维生素与蛋白质的中等紧密 1:1 摩尔复合物形式循环。RBP4 主要在肝脏中合成，但也由脂肪组织产生，并与较大的蛋白质转甲状腺素蛋白（TTR）结合而循环，这有助于增加其分子量，从而避免其被肾小球滤过消除。本文报道了从血浆、尿液和羊水天然缺乏结合视黄醇的人 RBP4 的高分辨率三维结构。在所有这些晶体中，我们都发现了一个脂肪酸分子结合在疏水性配体结合位点中，这一结果通过质谱测量得到了证实。此外，我们还报告了人全视黄醇结合蛋白 RBP4 以及与棕榈酸和月桂酸饱和的蛋白质的 1.5Å 分辨率结构，并讨论了脂肪酸和视黄醇与蛋白质的相互作用。
