NEW PERSPECTIVES ON THE STRUCTURE AND FUNCTION OF TRANSFERRINS
NEW PERSPECTIVES ON THE STRUCTURE AND FUNCTION OF TRANSFERRINS
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DOI：
10.1016/0162-0134(92)84061-q
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发表时间：
1992-08-15
影响因子：
3.9
通讯作者：
LINDLEY, PF
中科院分区：
文献类型：
--
作者：
BAKER, EN;LINDLEY, PF
根据最近的 X 射线晶体结构测定讨论了转铁蛋白的结构-功能关系。采用常见的折叠模式为两个叶，每个叶包含两个域；这使得铁能够紧密但可逆地结合。铁的吸收和释放涉及打开和关闭结合裂缝的大量结构域运动。铁结合位点相似，现在可以理解与每种 Fe3+ 结合的 CO32- 阴离子的关键作用：铁结合位点附近的结构差异表明血清转铁蛋白和乳铁蛋白结合特性不同的原因。聚糖部分似乎不会影响蛋白质结构或金属结合特性；它们在 X 射线分析中并未清晰可见，但已被建模。 Cu2+ 和草酸取代乳铁蛋白的晶体结构说明了不同金属和阴离子的调节； Al3+ 结合特别令人感兴趣。转铁蛋白受体与转铁蛋白、黑素转铁蛋白和无脊椎动物转铁蛋白（两者均具有缺陷的 C 末端结合位点）相互作用的新结果强调了两个叶之间可能存在的功能差异。转铁蛋白和乳铁蛋白的位点特异性突变体的出现为探索铁结合、铁释放和受体结合的结构决定因素提供了机会。
Structure-function relationships for transferrins are discussed in the light of recent X-ray crystal structure determinations. A common folding pattern into two lobes, each comprising two domains is adopted; this allows the tight, but reversible binding of iron. Uptake and release of iron involve substantial domain movements which open and close the binding clefts. The iron binding sites are similar and the key role of the CO32- anion bound with each Fe3+ can now be understood: structural differences near the iron binding sites suggest reasons for the different binding properties of serum transferrin and lactoferrin. The glycan moieties do not appear to affect the protein structure or metal binding properties; they are not clearly seen in the X-ray analyses but have been modelled. The accommodation of different metals and anions is illustrated by the crystal structures of Cu2+ and oxalate-substituted lactoferrins; Al3+ binding is of particular interest. New results on transferrin-receptor interactions with transferrin, and melanotransferrin and an invertebrate transferrin (both of which have defective C-terminal binding sites), emphasize possible functional differences between the two lobes. The availability of site-specific mutants of both transferrin and lactoferrin now offers the opportunity to probe the structural determinants of iron binding, iron release, and receptor binding.