IRON-APOFERRITIN--EFFECT & STRUCTURE OF SUBUNIT DIMERS
铁-脱铁铁蛋白--效应
基本信息
- 批准号:3286062
- 负责人:
- 金额:$ 9.16万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1985
- 资助国家:美国
- 起止时间:1985-08-01 至 1989-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Ferritin, a metalloprotein which stores iron in a bioavailable form,
overcomes the low solubility (10-18M) of iron in living systems. Small
amounts of ferritin occur in all cells of higher organisms, providing iron
for proteins of DNA synthesis, electron transport, and oxygen activation
and transport, while large amounts occur in specialized cells of iron
storage, e.g. liver, spleen, and red cells of embryo. Pathological
conditions occur when iron stores are low or are overloaded.
Superimposed on a highly conserved sequence are cell-specific features of
ferritin sequence and structure which may relate to function and/or
regulation. Ferritin structure could be further modified by cytoplasmic
components leading to functional changes. We have recently identified such
a change: ferritin subunit dimer crosslinks, a posttranslational
modification of ferritin, appear to regulate the iron content of ferritin
in vivo. The observation is the first identified, natural structural
modification related to the iron storage function of ferritin, to our
knowledge. Crosslinking with F2DNB replicates the effect. The structural
requirements for crosslinks (which are not -S-S) will be examined in terms
of the identity of the linked amino acids, the sequence and subunit
restrictions (by sequence analysis and comparison to known subunit
sequences), the sequences recognized by monoclonal antibodies sensitive to
the presence of crosslinks, the biosynthetic pathway of crosslink formation
(H-3-leucine pulse labeling) and cytoplasmic components which may influence
crosslinks (transpeptidases? ascorbate?). Cloned ferritin cDNA from lamb
spleen or other sources will be prepared and used to gain information about
the sequence and regulation of ferritin mRNA related to crosslinks. The
functional effect of crosslinks will be measured as the effect of
crosslink-sensitive monoclonal antibodies on iron uptake and release in
vitro and as the effect of crosslinks on Fe-protein interactions,
phosphate-Fe-protein interactions, and iron core structure, using X-ray
absorption spectroscopy (EXAFS and XANES). The results will be important
in understanding the molecular basis for pathologically altered iron
storage, e.g. iron deficiency anemia, hemochromatosis, thalassemia, and
cirrhosis, as well as understanding the relationship among cell-specific
features of protein structure, cytoplasmic modifying agents, and regulation
of function.
铁蛋白,一种以生物可利用形式储存铁的金属蛋白,
克服了铁在生物体系中溶解度低(10- 18 M)的缺点。 小
大量的铁蛋白存在于高等生物的所有细胞中,
负责DNA合成、电子传递和氧活化的蛋白质
和运输,而大量发生在专门的细胞铁
储存,例如肝脏、脾脏和胚胎的红细胞。 病理
当铁存储量低或过载时,会出现这种情况。
叠加在高度保守序列上的是细胞特异性特征,
铁蛋白序列和结构可能与功能和/或
调控 铁蛋白的结构可以进一步被细胞质修饰,
导致功能变化的组件。 我们最近发现,
a变化:铁蛋白亚基二聚体交联,翻译后
铁蛋白的修饰,似乎可以调节铁蛋白的铁含量
in vivo. 这是第一个被确认的,
与铁蛋白的铁储存功能相关的修饰,
知识 用F2 DNB交联复制了该效果。 结构性
交叉连接(不是-S-S)的要求将根据以下方面进行审查:
连接的氨基酸的身份,序列和亚基
限制(通过序列分析和与已知亚基的比较
序列),由对以下敏感的单克隆抗体识别的序列:
交联的存在,交联形成的生物合成途径
(H-3-亮氨酸脉冲标记)和细胞质成分,可能影响
交联(转肽酶?抗坏血酸盐?)。 克隆的羔羊铁蛋白cDNA
脾脏或其他来源将被准备并用于获得关于
与交联相关的铁蛋白mRNA的序列和调控。 的
交联的功能效应将被测量为
交联敏感性单克隆抗体对铁摄取和释放的影响
体外和作为交联对铁-蛋白质相互作用的影响,
磷酸盐-铁-蛋白质相互作用和铁核心结构,使用X射线
吸收光谱(EXAFS和XANES)。 结果会很重要
在理解病理改变的铁的分子基础
储存,例如缺铁性贫血、血色素沉着症、地中海贫血,以及
肝硬化,以及了解细胞特异性
蛋白质结构特征、细胞质修饰剂和调控
的功能。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ELIZABETH C THEIL其他文献
ELIZABETH C THEIL的其他文献
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{{ truncateString('ELIZABETH C THEIL', 18)}}的其他基金
Workshop on BioIron in Thalassemia, Sickle Cell Disease and Hemochromatosis
生物铁治疗地中海贫血、镰状细胞病和血色病研讨会
- 批准号:
6702966 - 财政年份:2004
- 资助金额:
$ 9.16万 - 项目类别:
Workshop on Biolron in Thalassemia & Sickle Cell Disease
Biolron 地中海贫血研讨会
- 批准号:
6555013 - 财政年份:2002
- 资助金额:
$ 9.16万 - 项目类别:
3 DIMENSIONAL STRUCTURE OF IRE IN FERRITIN MRNA, STUDIED BY NMR SPECTROSCOPY
通过核磁共振波谱研究铁蛋白 mRNA 中 IRE 的三维结构
- 批准号:
6309021 - 财政年份:2000
- 资助金额:
$ 9.16万 - 项目类别:
Ferritin and Iron Nutrition in Health and Disease
健康和疾病中的铁蛋白和铁营养
- 批准号:
6436336 - 财政年份:1998
- 资助金额:
$ 9.16万 - 项目类别:
FERRITIN AND IRON DEFICIENCY--A NEW LOOK AT THE PROBLEM
铁蛋白和缺铁——对问题的新看法
- 批准号:
2901238 - 财政年份:1998
- 资助金额:
$ 9.16万 - 项目类别:
FERRITIN AND IRON DEFICIENCY--A NEW LOOK AT THE PROBLEM
铁蛋白和缺铁——对问题的新看法
- 批准号:
2797653 - 财政年份:1998
- 资助金额:
$ 9.16万 - 项目类别:
FERRITIN AND IRON DEFICIENCY--A NEW LOOK AT THE PROBLEM
铁蛋白和缺铁——对问题的新看法
- 批准号:
6184363 - 财政年份:1998
- 资助金额:
$ 9.16万 - 项目类别:
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