Biomimetic Reagents that Promote Membrane Protein Stability (RMI)

促进膜蛋白稳定性 (RMI) 的仿生试剂

• 批准号: 7478762
• 负责人: PHILIP D LAIBLE
• 金额: $ 81.29万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-23 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7478762
• 关键词: Biomimetic; Reagents; Promote; Membrane; Protein

DESCRIPTION (provided by applicant): Proteins sequestered within cellular membranes perform a variety of tasks that are critical for the viability of healthy cells. As such, membrane proteins play pivotal roles in disease and represent the majority of drug targets. Detailed structural information for membrane proteins is exceedingly scarce, due in large part to the inability to produce quantities of native, functional material that is suitable for structure determination. The objective of this program project is to develop and implement biomimetic reagents that promote stability and crystallization of membrane proteins. This objective will be met by integrating investigators from Argonne National Laboratory (multiple groups from different divisions), the University of Wisconsin, and deCODE biostructures, Inc. into a highly multidisciplinary team of scientists with complementary expertise in biochemistry, synthetic chemistry, biophysics, immunology, and materials science. The innovations to be explored within this program project include: (1) development and implementation of a membrane protein crystallization strategy that circumvents the need for detergent solubilization, (2) evaluation, design, and use of new surfactants that improve upon and replace traditional detergents, (3) selection and production of affinity reagents that assist in the stabilization, purification, and/or crystallization of functional forms of membrane proteins, and (4) the design and application of synthetic amphiphilic nanomaterials (complex fluids) for the stabilization of membrane proteins and the production of ordered arrays that yield structural information. These projects will be supported by a core facility for membrane protein production (expression, purification, and functional characterization). Initially, we will use a set of well-characterized membrane proteins as a testing ground for the development and implementation of innovative reagents, methods, and approaches to the problem of producing stable, functional membrane proteins that are suitable for crystallization and structure determination experiments in nanomaterials. In later years, techniques emerging from the project will be applied to and adjusted for a broader and more challenging range of membrane protein targets. The insights gained from early successes and failures should allow an intelligent and effective approach to a more demanding, intricate, and functionally diverse set of membrane proteins and membrane protein complexes.

描述（由申请人提供）：隔离在细胞膜内的蛋白质执行对健康细胞的活力至关重要的多种任务。因此，膜蛋白在疾病中发挥着关键作用，并代表了大多数药物靶点。膜蛋白的详细结构信息极其稀缺，这在很大程度上是由于无法大量生产适合结构测定的天然功能材料。 该计划项目的目标是开发和实施促进膜蛋白稳定性和结晶的仿生试剂。这一目标将通过将来自阿贡国家实验室（来自不同部门的多个小组）、威斯康星大学和 deCODE biostructures, Inc. 的研究人员整合到一个高度多学科的科学家团队中来实现，该团队在生物化学、合成化学、生物物理学、免疫学方面具有互补的专业知识和材料科学。 该计划项目要探索的创新包括：(1) 开发和实施膜蛋白结晶策略，避免洗涤剂溶解的需要，(2) 评估、设计和使用新型表面活性剂，以改进和取代传统洗涤剂，（3）选择和生产有助于稳定、纯化和/或结晶膜蛋白功能形式的亲和试剂，以及（4）合成两亲性纳米材料（复杂流体）的设计和应用膜蛋白的稳定性和产生结构信息的有序阵列的产生。这些项目将得到膜蛋白生产（表达、纯化和功能表征）核心设施的支持。最初，我们将使用一组充分表征的膜蛋白作为开发和实施创新试剂、方法和途径的试验场，以解决生产稳定、功能性膜蛋白的问题，这些膜蛋白适用于结晶和结构测定实验。纳米材料。在接下来的几年中，该项目中出现的技术将被应用于更广泛和更具挑战性的膜蛋白靶标范围并进行调整。从早期的成功和失败中获得的见解应该可以提供一种智能且有效的方法来处理要求更高、更复杂且功能多样化的膜蛋白和膜蛋白复合物。