Mizutani Kimihiko, Toyoda Mayuko, Mikami Bunzo
Laboratory of Applied Structural Biology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
Biochim Biophys Acta. 2012 Mar;1820(3):203-11. doi: 10.1016/j.bbagen.2011.08.003. Epub 2011 Aug 9.
Transferrins are a group of iron-binding proteins including serum transferrin, lactoferrin and ovotransferrin.
The structures of transferrins are discussed.
The typical transferrin molecules are folded into two homologous lobes. X-ray crystallography revealed that each lobe is further divided into two similarly sized domains, and that an iron-binding site is contained within the inter-domain cleft. The six iron coordination sites are occupied by four residues and a bidentate carbonate anion.
The structures of the apo- and holo-forms revealed that the transferrins undergo a large-scale conformational change upon the uptake and release of irons: domains rotate as rigid bodies around a screw axis passing through inter-domain contacts. The iron-release mechanism of transferrin N-lobe is also revealed by X-ray crystallography; two basic residues in two domains form an unusual hydrogen bond in neutral pH, and the bond should be broken and facilitate iron release at a low pH of the endosome. For ovotransferrin, the iron release kinetics of two lobes correspond well with the numbers of anion binding sites found in crystal structures. The structures of transferrins bound to other metals revealed that the flexibility of the transferrin structure allows the ability to bind to other metals. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders.
转铁蛋白是一类铁结合蛋白，包括血清转铁蛋白、乳铁蛋白和卵转铁蛋白。
讨论了转铁蛋白的结构。
典型的转铁蛋白分子折叠成两个同源叶。X射线晶体学表明，每个叶进一步分为两个大小相似的结构域，且在结构域间裂隙中含有一个铁结合位点。六个铁配位位点由四个残基和一个双齿碳酸根阴离子占据。
脱铁和全铁形式的结构表明，转铁蛋白在摄取和释放铁时会发生大规模构象变化：结构域围绕穿过结构域间接触点的螺旋轴作为刚体旋转。X射线晶体学还揭示了转铁蛋白N叶的铁释放机制；两个结构域中的两个碱性残基在中性pH下形成一个不寻常的氢键，而在内涵体的低pH下该键应断裂并促进铁释放。对于卵转铁蛋白，两个叶的铁释放动力学与晶体结构中发现的阴离子结合位点数量非常吻合。与其他金属结合的转铁蛋白结构表明，转铁蛋白结构的灵活性使其能够结合其他金属。本文是名为“转铁蛋白：铁运输和紊乱的分子机制”的特刊的一部分。
