在人类线粒NEET的 (Cys) 3(His) 1-协调 [2Fe-2S] 集群中结合histidine
Michelle M Dicus1, Andrea Conlan, Rachel Nechushtai
1Department of Chemistry, University of California, Davis, California 95616, USA.
Journal of the American Chemical Society
|January 27, 2010
概括
人类mitoNEET是一种铁硫蛋白,其 [2Fe-2S] 集群结构使用先进的电子偏磁共振光谱学阐明. 这揭示了其电子状态和相互作用的关键细节,对于理解其功能和药物结合至关重要.
科学领域:
- 生物化学 生物化学
- 生物物理学的生物物理.
- 频谱学是一种光谱学.
背景情况:
- 人类mitoNEET是一种含有 [2Fe-2S] 集群的外层线粒体膜蛋白.
- 它的功能在很大程度上是未知的,但它与 thiazolidinedione 糖尿病药物相互作用.
- [2Fe-2S] 集群具有不寻常的Cys(3)His(1) 结合,其中histidine在集群属性中发挥着关键作用.
研究的目的:
- 为了研究人类mitoNEET中的 [2Fe-2S] 集群的结构和电子特性.
- 为了描述星团在其降低的偏磁状态 (S = 1/2) 中的特征.
- 提供光谱参数,可以报告由于pH值和药物结合而导致的集群变化.
主要方法:
- 多频和多技术的电子偏磁共振 (EPR) 光谱.
- 采用了连续波 (CW),电子自旋回声封膜调制 (ESEEM),脉冲电子核双共振 (ENDOR) 和超精细亚级相关性 (HYSCORE) 的技术.
- 用同位素标记 (14N和15N) 的mitoNEET的光谱使用模拟和最小正方形匹配进行了分析.
主要成果:
- 对于缩小的[Fe(2+) Fe(3+) ]集群,确定了一个罗姆比克g张量 (2.007,1.937,1.897).
- 解决了结合基丁 (N(delta)) 的超细张量和四极张量,从而可以推断出相对于集群的g张量方向.
- 观察到一个弱合的 (可能是histidine N(epsilon)) 和集群间双极合的证据.
- 集群存在于一个价值局部状态,Fe ((2+) 与histidine结合.
结论:
- 使用EPR光谱学确定了mitoNEET [2Fe-2S]星团的详细结构和电子参数.
- 突出了His连接体在集群性质和价值定位中的作用.
- 确定的参数可以作为未来关于mitoNEET通过pH和药物相互作用的功能调节的研究的基线.
相关概念视频
Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Metal-Ligand Bonds
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
Gene Families
Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Electron Transport Chain: Complex I and II
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
Histone Variants at the Centromere
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3 variants are also...
Tagging and Fusion Proteins
Proteins are involved in several cellular processes and biochemical reactions. Analyzing a specific protein of interest requires it to be isolated from the other proteins in the cell. This is achieved by overexpressing the specific gene in a suitable host to produce large quantities of the target protein. A tag or label is recombined with the gene to produce a fusion protein containing the target protein and the tag. The tags on these fusion proteins can then be used for easy detection and...


