Levina Aviva, Wang Boer, Lay Peter A
School of Chemistry, University of Sydney, Sydney, NSW 2006, Australia.
Sydney Analytical, University of Sydney, Sydney, NSW 2006, Australia.
Gels. 2021 Dec 27;8(1):19. doi: 10.3390/gels8010019.
Transferrin (Tf) is a crucial transporter protein for Fe(III), but its biological role in binding other metal ions and their delivery into cells remain highly controversial. The first systematic exploration of the effect of non-Fe(III) metal ion binding on Tf conformation has been performed by urea-polyacrylamide gel electrophoresis (urea-PAGE), which is commonly used for nucleic acids but rarely for proteins. Closed Tf conformation, similar to that caused by Fe(III)-Tf binding, was formed for In(III), V(III) or Cr(III) binding to Tf. In all these cases, metal distribution between Tf lobes and/or the rate of metal release under acidic conditions differed from that of Fe(III)-Tf. By contrast, Ga(III) and V(IV) did not form closed Tf conformation under urea-PAGE conditions. Apart from Fe(III), only In(III) was able to increase the proportion of closed Tf conformation in whole serum. These results suggest that Tf is unlikely to act as a natural carrier of any metal ion, except Fe(III), into cells but can reduce toxicity of exogenous metal ions by binding them in serum and preventing their entry into cells.
转铁蛋白（Tf）是一种至关重要的铁（III）转运蛋白，但其在结合其他金属离子以及将这些金属离子转运进细胞中的生物学作用仍极具争议。通过尿素 - 聚丙烯酰胺凝胶电泳（urea - PAGE）首次对非铁（III）金属离子结合对转铁蛋白构象的影响进行了系统探索，这种方法通常用于核酸分析，很少用于蛋白质分析。当铟（III）、钒（III）或铬（III）与转铁蛋白结合时，会形成类似于铁（III） - 转铁蛋白结合所导致的封闭型转铁蛋白构象。在所有这些情况下，转铁蛋白两个叶之间的金属分布和/或酸性条件下的金属释放速率与铁（III） - 转铁蛋白的情况不同。相比之下，在尿素 - PAGE条件下，镓（III）和钒（IV）不会形成封闭型转铁蛋白构象。除了铁（III）之外，只有铟（III）能够增加全血清中封闭型转铁蛋白构象的比例。这些结果表明，除了铁（III）之外，转铁蛋白不太可能作为任何金属离子进入细胞的天然载体，但它可以通过在血清中结合外源金属离子并阻止其进入细胞来降低其毒性。
