Davis Jonathan P, Shettigar Vikram, Tikunova Svetlana B, Little Sean C, Liu Bin, Siddiqui Jalal K, Janssen Paul M L, Ziolo Mark T, Walton Shane D
Davis Heart and Lung Research Institute and Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, OH, USA.
Davis Heart and Lung Research Institute and Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, OH, USA.
Arch Biochem Biophys. 2016 Jul 1;601:4-10. doi: 10.1016/j.abb.2016.02.007. Epub 2016 Feb 18.
Throughout history, muscle research has led to numerous scientific breakthroughs that have brought insight to a more general understanding of all biological processes. Potentially one of the most influential discoveries was the role of the second messenger calcium and its myriad of handling and sensing systems that mechanistically control muscle contraction. In this review we will briefly discuss the significance of calcium as a universal second messenger along with some of the most common calcium binding motifs in proteins, focusing on the EF-hand. We will also describe some of our approaches to rationally design calcium binding proteins to palliate, or potentially even cure cardiovascular disease. Considering not all failing hearts have the same etiology, genetic background and co-morbidities, personalized therapies will need to be developed. We predict designer proteins will open doors for unprecedented personalized, and potentially, even generalized medicines as gene therapy or protein delivery techniques come to fruition.
纵观历史,肌肉研究带来了众多科学突破,为更全面地理解所有生物过程提供了深刻见解。其中最具影响力的发现之一可能是第二信使钙的作用及其众多的处理和传感系统,这些系统通过机械方式控制肌肉收缩。在本综述中,我们将简要讨论钙作为通用第二信使的重要性,以及蛋白质中一些最常见的钙结合基序,重点是EF手结构。我们还将描述我们合理设计钙结合蛋白以缓解甚至可能治愈心血管疾病的一些方法。考虑到并非所有衰竭心脏都有相同的病因、遗传背景和合并症,需要开发个性化疗法。我们预测,随着基因治疗或蛋白质递送技术的成熟,设计蛋白将为前所未有的个性化甚至可能的通用药物打开大门。