Conformational change in NSS transporters

摘要 我们的目标是了解运输蛋白大家族的运动机制。 小分子和离子穿过生物膜。近年来，这一点变得明显起来。 许多运输蛋白家族在结构水平上是相关的。传送者 蛋白质负责在细胞内移动各种底物分子。 膜。它们调节大脑中神经递质、糖和氨基酸的重新摄取。 肾和肠的转运，碘在甲状腺的转运，以及许多其他重要的 对健康和疾病至关重要的运输过程。这些运输机 所有家族都基于一个蛋白质折叠，其中包含两个结构相似的相反重复序列 相对于膜的方向。最近的结构性证据表明，运输 需要4-螺旋束在蛋白质内重新排列的构象变化 结构。然而，这些转运蛋白在细胞内积累底物的能力 使用离子的耦合运动是以前的研究没有解决的另一个问题。这个 该项目的具体目标是使用生化、生物物理和计算方法。 测试所提出的机制，并了解底物和离子的结合如何触发 与束的运动和随后的开放有关的构象变化 以及关闭渗透通道。

Abstract Our goal is to understand the mechanism by which a large family of transport proteins moves small molecules and ions across biological membranes. In recent years it has become apparent that many families of transport proteins are related at the structural level. The transporter proteins are responsible for moving a wide variety of substrate molecules across cell membranes. They mediate neurotransmitter re-uptake in the brain, sugar and amino acid transport in kidney and intestine, iodide transport in thyroid, and many other important transport processes that are critically important in health and disease. These transporter families are all based on a protein fold containing two structurally similar repeats in opposite orientations relative to the membrane. Recent structural evidence indicates that transport requires a conformational change in which a 4-helix bundle rearranges within the protein structure. However, the ability of these transporters to accumulate substrates within the cell using the coupled movement of ions is a separate issue not addressed by previous studies. The specific aims of this project are to use biochemical, biophysical and computational approaches to test proposed mechanisms, and to understand how binding of substrate and ions can trigger conformational changes relating to the movement of the bundle and the consequent opening and closing of permeation pathways.