Evolution and function of vertebrate globins

脊椎动物珠蛋白的进化和功能

• 批准号: 257057960
• 负责人: Professor Dr. Thorsten Burmester
• 金额: --
• 依托单位: Arbeitsbereich Molekulare Tierphysiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/257057960?language=en
• 关键词: Evolution; function; vertebrate; globins

Globins are small iron-heme proteins that bind oxygen and thus play an important role in the animal's respiration and oxidative energy production. Hemoglobin and myoglobin are among the best investigated proteins in biomedical sciences, and are a model system to study protein function and evolution. In recent years, our studies led to the identification of six additional globin types in vertebrate (androglobin, neuroglobin, cytoglobin, globin E, globin X and globin Y). The functions of these "novel" globins are still poorly understood and subject of the present application. Analyses of globin relationships, globin gene repertoire and gene order (synteny) allow delineating the evolutionary history of globins. We will specifically focus on the globins of the lamprey, which provide information on the early evolution of vertebrate globins, and of turtles, which possess all eight globin types and thus allow studying their sub-functionalisation. Expression analyses in these species will provide clues about the tissue- and cell-specific roles in both species. Functional analyses will be carried out in stably transfected vertebrate cell lines. The ability of different globins to augment mitochondrial respiration, to mediate tolerance towards hypoxia and reactive oxygen (ROS), to protect lipids, to protect from apoptosis and their roles in the generation of ROS and NO will be tested. This comparative approach will allow evaluating different hypothesis of globin functions and hopefully allow the identification the physiological role of each globin. Kinetic and structural data will be obtained for selected globins. The combination of the results from the phylogenetic and functional experiments will allow us to trace the changes of physiological roles that occurred in the vertebrate globin family during evolution.

珠蛋白是一种小的铁-血红素蛋白，可以结合氧气，因此在动物的呼吸和氧化能量产生中发挥重要作用。血红蛋白和肌红蛋白是生物医学中研究最多的蛋白质之一，是研究蛋白质功能和进化的模型系统。近年来，我们的研究导致在脊椎动物中鉴定出另外六种珠蛋白类型(雄球蛋白、脑红蛋白、细胞球蛋白、珠蛋白E、珠蛋白X和珠蛋白Y)。这些“新奇的”珠蛋白的功能仍然很少被理解，也是本申请的主题。对珠蛋白关系、珠蛋白基因谱系和基因顺序(同时性)的分析可以描绘珠蛋白的进化史。我们将特别关注七鳗鱼的球蛋白，它提供了脊椎动物球蛋白的早期进化信息，以及海龟的球蛋白，它们拥有所有八种球蛋白类型，因此可以研究它们的亚功能。对这些物种的表达分析将提供关于这两个物种组织和细胞特定角色的线索。功能分析将在稳定转基因的脊椎动物细胞系中进行。不同的珠蛋白增强线粒体呼吸的能力，介导对缺氧和活性氧(ROS)的耐受，保护脂质，防止细胞凋亡的能力，以及它们在ROS和NO产生中的作用将被测试。这种比较方法将允许评估不同的珠蛋白功能假说，并有望识别每种珠蛋白的生理作用。将获得选定珠蛋白的动力学和结构数据。将系统发育和功能实验的结果结合起来，将使我们能够追踪脊椎动物珠蛋白家族在进化过程中发生的生理角色的变化。