Structural characterization of rod phosphodiesterase 6 using mass spectrometry

有了这个奖项，生命过程的化学计划是支持博士的合作研究。美国新罕布什尔大学的Chu Feixia和Rick Cote研究了一种中心光导效应酶——光受体磷酸二酯酶-6 （PDE6）的结构特征。PDE6调节光感受器外段的cGMP水平，决定脊椎动物光感受器光反应的幅度、持续时间和适应性。本研究旨在阐明PDE6变构调节因子的结构决定因素、动态PDE6信号复合物的空间组织和分子识别。本研究是跨学科的，涉及质谱和蛋白质生物化学的结合，以研究控制PDE6激活/失活周期的潜在结构要素。这项工作有望揭示视觉周期和分子水平的关键事件，重点关注参与信号转导的关键蛋白质。从更广泛的意义上说，这项工作有望导致检测蛋白质构象变化的策略和方法，特别是在结构异质系统中，具有潜在的适用性，技术上具有挑战性的膜蛋白和蛋白质复合物。该项目的跨学科性质将使本科生、研究生和博士后实习生在生物化学、基于质谱的蛋白质组学和结构分析的界面上获得广泛的技能。除了拟议的研究之外，研究团队人员将继续参与新罕布什尔大学化学/生物界面的教育和推广工作。

With this award, the Chemistry of Life Processes Program is supporting the collaborative research of Drs. Feixia Chu and Rick Cote at University of New Hampshire on the structural characterization of a central phototransduction effector enzyme, photoreceptor phosphodiesterase-6 (PDE6). PDE6 modulates cGMP levels in the photoreceptor outer segment to define the amplitude, duration and adaptation of the photoresponse in vertebrate photoreceptors. This study aims to elucidate the structural determinants of PDE6 allosteric regulators, the spatial organization and molecular recognition of the dynamic PDE6 signaling complex. This research is interdisciplinary, involving the combination of mass spectometry and protein biochemistry to study the underlying structural elements that govern the PDE6 activation/deactivation cycle.This work is expected to both shed light on key events in the visual cycle and the molecular level, focusing on a key protein involved in signal transduction. In a more general sense, the work is expected to lead to strategies and methods to detect protein conformational change, especially in structurally heterogeneous systems, with potentially applicability to technically challenging membrane proteins and protein complexes. The interdisciplinary nature of this project will expose undergraduate and graduate students and a postdoctoral trainee to a broad set of skills at the interface of biochemistry, mass spectrometry-based proteomics and structural analysis. In addition to the proposed research, the research team personnel will continue to participate in education and outreach efforts at the Chemistry/Biology interface at the University of New Hampshire.