STRUCTURE AND DYNAMICS OF EMRE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 转运蛋白发挥着关键作用，积极中继分子穿过膜屏障，并对他们的浓度梯度。该项目的目标是了解这些蛋白质如何在分子水平上起作用。这需要详细的结构知识和动态信息，包括结构变化的时间尺度、幅度和方向，以便构建蛋白质的“电影”。NMR是唯一适合解决这些问题，因为动力学数据与化学位移同时测量，原子分辨率结构的直接表现。小的多药耐药外排蛋白，EmrE，提供了一个理想的模型系统，以检查分子运动是如何耦合到一个定向的生物反应。EmrE偶联质子输入以驱动多环芳烃阳离子输出。大肠杆菌，从而赋予对这类药物的抗性。虽然细节尚不清楚，但蛋白质构象变化必须发生才能正确转运，允许响应底物结合而交替进入膜的两侧。本计画主要探讨在EmrE中，结合与转运的关键耦合机制及所提出的转运模式。这些知识将有助于努力打击多药耐药转运蛋白对细菌抗生素耐药性的贡献。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Transporter proteins perform a critical role, actively relaying molecules across the membrane barrier and against their concentration gradient. The goal of this project is to understand how these proteins act on a molecular level. This requires detailed structural knowledge coupled with dynamic information, including the timescale, amplitude and direction of structural changes, in order to build a 'movie' of the protein in action. NMR is uniquely suited to address these questions since kinetic data are measured simultaneously with the chemical shift, a direct manifestation of atomic resolution structure. The small multidrug resistance efflux protein, EmrE, provides an ideal model system to examine how molecular motion is coupled to a directed biological response. EmrE couples proton import to drive polyaromatic cation export in E. coli, thus conferring resistance to drugs of this type. Although the details are not known, protein conformational change must occur for proper transport, allowing alternating access to either side of the membrane in response to substrate binding. This project investigates the proposed transport model and the mechanism of the critical coupling between binding and transport in EmrE. This knowledge will aid efforts to combat the contribution of multidrug resistance transporters to bacterial antibiotic resistance.