Investigations into the molecular basis of regulation of ATP-sensitive K+ chaannels by SUR proteins, members of ABC transporters

研究 ABC 转运蛋白成员 SUR 蛋白调节 ATP 敏感 K 通道的分子基础

• 批准号: 357118-2009
• 负责人: Kanelis, Voula
• 金额: $ 2.19万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=528073
• 关键词: Investigations; into; molecular; basis; regulation

The sulphonyl urea (SUR) protein family is a member of a large superfamily of membrane proteins found in all organisms. By utilizing the energy of ATP, known as the energy currency of the cell, these proteins bind compounds at the membrane and/or actively transport solutes into and out of the cell. Proper regulation of this process is essential, as many genetic diseases, including cystic fibrosis and adrenoleukodystrophy, result from dysfunction of different proteins in this ubiquitous protein superfamily. SUR proteins are part of a large protein complex that functions as a potassium channel and use ATP to regulate opening and closing of the channel pore. Regulation of the protein that forms the channel pore (called Kir6.x) by the SURs is essential. Dysfunction of SUR proteins that affects their ability to use ATP, to adopt their cognate three-dimensional structure, and to interact with Kir6.x in the channel complex result in cardiovascular disorders and pancreatic diseases related to insulin production.

磺酰尿素(SUR)蛋白家族是存在于所有生物中的膜蛋白超家族中的一员。通过利用被称为细胞能量流通的三磷酸腺苷的能量，这些蛋白质在膜上结合化合物和/或主动地将溶质运入和运出细胞。这一过程的适当调控是至关重要的，因为许多遗传性疾病，包括囊性纤维化和肾上腺脑白质营养不良，都是由于这个无处不在的蛋白质超家族中不同蛋白质的功能障碍造成的。SuR蛋白是一个大型蛋白质复合体的一部分，该复合体具有钾通道的功能，并使用ATP来调节通道孔的打开和关闭。SURS对形成通道孔(称为Kir6.x)的蛋白质的调节是必不可少的。SuR蛋白的功能障碍影响其利用ATP的能力，采用其同源的三维结构，并与通道复合体中的Kir6.x相互作用，导致心血管疾病和与胰岛素产生相关的胰腺疾病。