CRYSTAL STRUCTURES OF MINER 1: THE REDOX-ACTIVE 2FE-2S PROTEIN CAUSATIVE IN WOLF

MINER 1 的晶体结构：狼体内氧化还原活性 2FE-2S 蛋白

• 批准号: 8362140
• 负责人: AINA COHEN
• 金额: $ 0.08万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362140
• 关键词: Aging; Amino Acids; Binding; Blindness; Code; Diabetes Mellitus; Endoplasmic Reticulum; Funding; Grant; Health; Human; Knock-out; Longevity; Mitochondrial Membrane Protein; Muscular Atrophy; National Center for Research Resources; Optic Atrophy; Outer Mitochondrial Membrane; Oxidation-Reduction; Principal Investigator; Proteins; R-factor; RNA Splicing; Radiation; Research; Research Infrastructure; Resolution; Resources; Source; Structure; Time; United States National Institutes of Health; Wolfram Syndrome; Wolves; Work; Zinc Fingers; cost; deafness; early onset; paralogous gene; resistance factors; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The endoplasmic reticulum protein Miner1 is essential for health and longevity. Mis-splicing of CISD2, which codes for Miner1, is causative in Wolfram Syndrome 2 (WFS2) resulting in early onset optic atrophy, diabetes mellitus, deafness and decreased lifespan. In knock-out studies, disruption of CISD2 leads to accelerated aging, blindness and muscle atrophy. In this work, the soluble region of human Miner1 was characterized and the crystal structure was solved to a resolution of 2.1 A (R-factor=17%). Although originally annotated as a zinc finger, Miner1 is a homodimer harboring two redox-active 2Fe-2S clusters, indicating for the first time an association of a redox-active FeS protein with WFS2. Each 2Fe-2S cluster is bound by a rare Cys(3)-His motif within a 17 amino acid segment. Miner1 is the first functionally different protein that shares the NEET fold with its recently identified paralog mitoNEET, an outer mitochondrial membrane protein.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 内质网蛋白矿工1对于健康和寿命至关重要。在WOLFRAM综合征2（WFS2）中，CISD2的错误切割是为矿工1编码的，导致早期发作视神经萎缩，糖尿病，糖尿病，耳聋和寿命降低。在敲除研究中，CISD2的破坏会导致衰老，失明和肌肉萎缩。在这项工作中，对人矿工1的可溶性区域进行了表征，并将晶体结构求解为2.1 a（R-factor = 17％）的分辨率。尽管最初被注释为锌指的矿工，但Miner1是一种具有两个氧化还原活性2FE-2S簇的同型二聚体，这首先表明氧化还原活性FES蛋白与WFS2的关联。每个2FE-2S群集在17个氨基酸段内受到罕见的Cys（3） - 他的基序。 Miner1是第一个在功能上不同的蛋白质，与最近确定的旁系同源物线粒体（一种外部线粒体膜蛋白）共享NEET褶皱。