Hempstead P D, Yewdall S J, Fernie A R, Lawson D M, Artymiuk P J, Rice D W, Ford G C, Harrison P M
Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, England.
J Mol Biol. 1997 May 2;268(2):424-48. doi: 10.1006/jmbi.1997.0970.
Mammalian ferritins are 24-mers assembled from two types of polypeptide chain which provide the molecule with different functions. H(eavy) chains catalyse the first step in iron storage, the oxidation of iron(II). L(ight) chains promote the nucleation of the mineral ferrihydrite enabling storage of iron(III) inside the protein shell. We report here the comparison of the three-dimensional structures of recombinant human H chain (HuHF) and horse L chain (HoLF) ferritin homopolymers, which have been refined at 1.9 A resolution. There is 53% sequence identity between these molecules, and the two structures are very similar, the H and L subunit alpha-carbons superposing to within 0.5 A rms deviation with 41 water molecules in common. Nevertheless, there are significant important differences which can be related to differences in function. In particular, the centres of the four-helix bundles contain distinctive groups of hydrophilic residues which have been associated with ferroxidase activity in H chains and enhanced stability in L chains. L chains contain a group of glutamates associated with mineralisation within the iron storage cavity of the protein.
哺乳动物铁蛋白是由两种类型的多肽链组装而成的24聚体，这两种多肽链赋予分子不同的功能。重链催化铁储存的第一步，即亚铁离子的氧化。轻链促进矿物水铁矿的成核，使铁离子能够储存在蛋白质外壳内。我们在此报告重组人重链铁蛋白（HuHF）和马轻链铁蛋白（HoLF）同聚物三维结构的比较，这两种结构已在1.9 Å分辨率下进行了优化。这些分子之间有53%的序列同一性，并且两种结构非常相似，重链和轻链亚基的α碳原子的均方根偏差在0.5 Å以内，共有41个水分子。然而，存在一些显著的重要差异，这些差异可能与功能差异有关。特别是，四螺旋束的中心包含独特的亲水性残基基团，这些基团与重链中的铁氧化酶活性以及轻链中的稳定性增强有关。轻链包含一组与蛋白质铁储存腔内矿化相关的谷氨酸。
