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: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=549959
• 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.

磺酰脲 (SUR) 蛋白家族是所有生物体中发现的膜蛋白大超家族的成员。通过利用被称为细胞能量货币的 ATP 能量，这些蛋白质将化合物结合在膜上和/或主动将溶质转运入和转运出细胞。对该过程的适当调节至关重要，因为许多遗传疾病，包括囊性纤维化和肾上腺脑白质营养不良，都是由这个普遍存在的蛋白质超家族中不同蛋白质的功能障碍引起的。 SUR 蛋白是大型蛋白质复合物的一部分，其功能相当于钾通道，并使用 ATP 调节通道孔的打开和关闭。 SUR 对形成通道孔的蛋白质（称为 Kir6.x）的调节至关重要。 SUR 蛋白的功能障碍会影响其使用 ATP、采用同源三维结构以及与通道复合物中的 Kir6.x 相互作用的能力，从而导致与胰岛素产生相关的心血管疾病和胰腺疾病。