Ferritin: the protein nanocage and iron biomineral in health and in disease.

Ferritin: the protein nanocage and iron biomineral in health and in disease.
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DOI:
10.1021/ic400484n
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发表时间:
2013-11-04
影响因子:
4.6
通讯作者:
Theil EC
Theil EC
中科院分区:
化学2区
文献类型:
--
作者:
Theil EC

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铁和氧化剂代谢的中心是铁蛋白超家族:具有 Fe2+ 离子通道的蛋白质笼和催化二 Fe/O 氧化还原中心,可启动笼中 Fe2O3 • H2O 的形成。铁蛋白纳米矿物质在蛋白质笼内启动,在笼腔内(直径 5 或 8 nm)生长。铁蛋白有助于正常的铁流动、维持铁辅因子合成的铁浓缩物、隔离入侵病原体的铁、氧化剂保护、氧化应激恢复,以及在铁过度积累的疾病中促进铁螯合策略。在真核铁蛋白中,生物矿物顺序/结晶度受到活性位点和矿物生长腔之间的成核通道的影响。动物铁蛋白笼独特地含有催化活性 (H) 和非活性 (L) 多肽亚基的混合物,具有不同的 Fe2+/O2 催化速率和矿物结晶度。例如,肝铁蛋白中相对较低的矿物质顺序与高百分比的 L 亚基一致,因此催化位点和成核通道的百分比较低。低矿物质顺序有利于铁的快速周转以及肝铁蛋白作为其他组织的一般铁源的生理作用。在这里,讨论了铁蛋白结构/功能/基因调控的当前概念,并与可能的治疗靶点相关,例如微型铁蛋白/Dps蛋白活性位点(感染中的选择性病原体抑制)、纳米笼孔(治疗性过度输血中的铁螯合)、mRNA非编码、IRE-核糖调节剂(治疗后使铁蛋白铁含量正常化) 超输血,以及作为蛋白质纳米血管来输送药物或传感器货物。
At the center of iron and oxidant metabolism is the ferritin superfamily: protein cages with Fe2+ ion channels and catalytic di- Fe/O redox centers that initiate formation of caged Fe2O3 • H2O. Ferritin nanominerals, initiated within the protein cage, grow inside the cage cavity (5 or 8 nm in diameter). Ferritins contribute to normal iron flow, maintenance of iron concentrates for iron cofactor syntheses, sequestration of iron from invading pathogens, oxidant protection, oxidative stress recovery and, in diseases where iron accumulates excessively, to iron chelation strategies. In eukaryotic ferritins, biomineral order/crystallinity is influenced by nucleation channels between active sites and the mineral growth cavity. Animal ferritin cages contain, uniquely, mixtures of catalytically active (H) and inactive (L) polypeptide subunits with varied rates of Fe2+/O2 catalysis and mineral crystallinity. The relatively low mineral order in liver ferritin, for example, coincides with a high % of L subunits, and, thus, a low % of catalytic sites and nucleation channels. Low mineral order facilitates rapid iron turnover and the physiological role of liver ferritin as a general iron source for other tissues. Here, current concepts of ferritin structure/function/genetic regulation are discussed and related to possible therapeutic targets such as mini-ferritin/Dps protein active sites (selective pathogen inhibition in infection), the nanocage pores (iron chelation in therapeutic hypertransfusion), the mRNA noncoding, IRE-riboregulator (normalizing ferritin iron content after therapeutic hypertransfusion, and as protein nanovessels to deliver medicinal or sensor cargo.
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