IRON-APOFERRITIN--EFFECT & STRUCTURE OF SUBUNIT DIMERS
IRON-APOFERRITIN--EFFECT & STRUCTURE OF SUBUNIT DIMERS
批准号:
3286062
负责人:
ELIZABETH C THEIL
金额:
$9.16万
依托单位国家:
美国
项目类别:
财政年份:
1985
资助国家:
美国
项目状态:
已结题
起止时间:
1985-08-01 至 1989-07-31
中文摘要
铁蛋白是一种金属蛋白,它以生物可利用的形式储存铁,
克服了铁在生命系统中的低溶解度(10-18M)。小的
大量的铁蛋白存在于高等生物的所有细胞中,提供铁
对于DNA合成、电子传递和氧激活的蛋白质
和运输,而大量存在于特殊的铁细胞中
储存,例如肝、脾和胚胎的红细胞。病理性的
当铁储备不足或超载时,就会出现这种情况。
叠加在高度保守的序列上的是细胞特有的特征
可能与功能和/或相关的铁蛋白序列和结构
监管。铁蛋白结构可通过细胞质进一步修饰
导致功能变化的组件。我们最近发现了这样的情况
变化:铁蛋白亚基二聚体交联体,一种翻译后
铁蛋白的修饰,似乎可以调节铁蛋白中的铁含量
在活体内。这种观察是第一次被识别的,自然的结构
与铁蛋白储铁功能有关的修饰,对我们的
知识。用F2DNB进行交联会复制这种效果。结构性的
交叉链接(不是S-S)的要求将从以下方面进行检查
连接的氨基酸、序列和亚基的同一性
限制条件(通过序列分析和与已知亚单位的比较
序列),由敏感的单抗识别的序列
交联物的存在,交联物形成的生物合成途径
(H-3-亮氨酸脉冲标记)和可能影响的细胞质成分
交联物(转肽酶?抗坏血酸?)羔羊铁蛋白基因的克隆
脾或其他来源将准备并用于获取关于
与交联剂相关的铁蛋白基因的序列和调控。这个
交联剂的功能效应将被测量为
交联剂敏感的单抗对铁摄取和释放的影响
在体外,由于交联剂对铁-蛋白质相互作用的影响,
磷酸盐-铁-蛋白质相互作用和铁核结构的X射线研究
吸收光谱(EXAFS和XANES)。结果将是重要的
了解病理性铁改变的分子基础
储存,如缺铁性贫血、血色素沉着症、地中海贫血和
以及了解细胞特异性之间的关系
蛋白质结构特征、细胞质修饰剂及其调控
功能的一部分。
英文摘要
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.
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会议论文
Workshop on BioIron in Thalassemia, Sickle Cell Disease and Hemochromatosis
-
批准号:6702966
-
项目类别:
-
资助金额:$2.55万
-
财政年份:2004
-
负责人:ELIZABETH C THEIL
-
依托单位:
Workshop on Biolron in Thalassemia & Sickle Cell Disease
-
批准号:6555013
-
项目类别:
-
资助金额:$1.45万
-
财政年份:2002
-
负责人:ELIZABETH C THEIL
-
依托单位:
IRON & OXYGEN BIOLOGY IN SCD, HH & BETA-THAL MICE
-
批准号:6381947
-
项目类别:
-
资助金额:$19.34万
-
财政年份:2000
-
负责人:ELIZABETH C THEIL
-
依托单位:
IRON & OXYGEN BIOLOGY IN SCH, HH & BETA-THAL MICE
-
批准号:6258562
-
项目类别:
-
资助金额:$19.34万
-
财政年份:2000
-
负责人:ELIZABETH C THEIL
-
依托单位:
IRON & OXYGEN BIOLOGY IN SCD, HH & BETA-THAL MICE
-
批准号:6517855
-
项目类别:
-
资助金额:$19.34万
-
财政年份:2000
-
负责人:ELIZABETH C THEIL
-
依托单位:
3 DIMENSIONAL STRUCTURE OF IRE IN FERRITIN MRNA, STUDIED BY NMR SPECTROSCOPY
-
批准号:6309021
-
项目类别:
-
资助金额:$2.74万
-
财政年份:2000
-
负责人:ELIZABETH C THEIL
-
依托单位:
Ferritin and Iron Nutrition in Health and Disease
-
批准号:6436336
-
项目类别:
-
资助金额:$34.77万
-
财政年份:1998
-
负责人:ELIZABETH C THEIL
-
依托单位:
FERRITIN AND IRON DEFICIENCY--A NEW LOOK AT THE PROBLEM
-
批准号:2901238
-
项目类别:
-
资助金额:$13.16万
-
财政年份:1998
-
负责人:ELIZABETH C THEIL
-
依托单位:
FERRITIN AND IRON DEFICIENCY--A NEW LOOK AT THE PROBLEM
-
批准号:2797653
-
项目类别:
-
资助金额:$13.78万
-
财政年份:1998
-
负责人:ELIZABETH C THEIL
-
依托单位:
FERRITIN AND IRON DEFICIENCY--A NEW LOOK AT THE PROBLEM
-
批准号:6184363
-
项目类别:
-
资助金额:$13.15万
-
财政年份:1998
-
负责人:ELIZABETH C THEIL
-
依托单位:
Ferritin and Iron Nutrition in Health and Disease
-
批准号:6686411
-
项目类别:
-
资助金额:$36.03万
-
财政年份:1998
-
负责人:ELIZABETH C THEIL
-
依托单位:
3 DIMENSIONAL STRUCTURE OF IRE IN FERRITIN MRNA, STUDIED BY NMR SPECTROSCOPY
-
批准号:6281479
-
项目类别:
-
资助金额:$5.83万
-
财政年份:1998
-
负责人:ELIZABETH C THEIL
-
依托单位:
Ferritin and Iron Nutrition in Health and Disease
-
批准号:6821367
-
项目类别:
-
资助金额:$37.01万
-
财政年份:1998
-
负责人:ELIZABETH C THEIL
-
依托单位:
Ferritin and Iron Nutrition in Health and Disease
-
批准号:6621749
-
项目类别:
-
资助金额:$34.2万
-
财政年份:1998
-
负责人:ELIZABETH C THEIL
-
依托单位:
3 DIMENSIONAL STRUCT OF IRE IN FERRITIN MRNA, STUDIED BY NMR SPECTROSCOPY
-
批准号:6251979
-
项目类别:
-
资助金额:$1.96万
-
财政年份:1997
-
负责人:ELIZABETH C THEIL
-
依托单位:
INTERNATIONAL CONFERENCE ON BIOLRON
-
批准号:2150353
-
项目类别:
-
资助金额:$1.5万
-
财政年份:1995
-
负责人:ELIZABETH C THEIL
-
依托单位:
METALS IN BIOLOGY GORDON CONFERENCE
-
批准号:2190539
-
项目类别:
-
资助金额:$0.6万
-
财政年份:1995
-
负责人:ELIZABETH C THEIL
-
依托单位:
IRON-APOFERRITIN--EFFECT & STRUCTURE OF SUBUNIT DIMERS
-
批准号:3286059
-
项目类别:
-
资助金额:$9.65万
-
财政年份:1985
-
负责人:ELIZABETH C THEIL
-
依托单位:
IRON-APOFERRITIN--EFFECT & STRUCTURE OF SUBUNIT DIMERS
-
批准号:3286064
-
项目类别:
-
资助金额:$11.04万
-
财政年份:1985
-
负责人:ELIZABETH C THEIL
-
依托单位:
IRON-APOFERRITIN--EFFECT & STRUCTURE OF SUBUNIT DIMERS
-
批准号:3286063
-
项目类别:
-
资助金额:$9.69万
-
财政年份:1985
-
负责人:ELIZABETH C THEIL
-
依托单位:
海外基金