The Transmembrane Protein Center

跨膜蛋白中心（TMPC）提议作为PSIBiology网络中的合作项目。TMPC研究团队已经组建起来，为结构基因组学的所有组成任务提供各种技能和经验。我们的集体经验表明，许多技术的应用将需要扩大成功的机会，与广泛的膜蛋白预期参与PSIBiology网络。该项目将为成功推进PSIBiology网络的目标提供所需的专业知识和领导力，包括向这一大规模努力的新参与者拓展。该团队包括具有膜蛋白表达、生产和表征经验的科学家，具有解决复杂膜蛋白结构的能力，并且在研究膜蛋白与其蛋白质伴侣和生物配体的相互作用方面有着良好的记录。该团队在使用生物信息学和生物分析技术方面有很强的基础。每位参与者都带来了膜蛋白功能的独特经验，包括分析开发，制备方法或纯化蛋白和活生物体的研究。强调将膜蛋白的生产用于结构测定与功能表征的力量相结合是我们中心的核心理念。TMPC的主要目标是确定本提案中阐述的每个独特目标类的基础结构。我们的第二个目标是建立一个高效的膜蛋白生产管道，以便逐步提高产量。TMPC希望提高其创建蛋白质变体的能力，改进基于功能和生物物理特征的筛选，并改进多种表达途径之间的分类，以找到产生感兴趣的蛋白质的最佳方法。重视小规模的净化筛选，并进一步将自动化融入到我们的工作中，将提高效率。结晶筛选的扩展选项、同步加速器的使用以及用于解决结构的软件的改进也将有助于提高实现PSI：生物学目标所需的吞吐量。

The Transmembrane Protein Center (TMPC) proposes to function as collaborative project within the PSIBiology Network. The TMPC research team has been assembled to provide diverse skills and experience in all constituent tasks of structural genomics. Our collective experience suggests that application of many techniques will be needed to expand the chances for success with the broad range of membrane proteins expected from participation in the PSIBiology Network. This project is well poised to provide the expertise and leadership needed to successfully advance the goals of the PSIBiology Network, including outreach to new participants in this large-scale endeavor. The assembled team includes scientists with experience in the expression, production, and characterization of membrane proteins, proven ability to solve structures of complicated membrane proteins, and a strong track record of studying the interactions of membrane proteins with their protein partners and biological ligands. The team has strong grounding in the use of bioinformatics and bioanalytical techniques. Every participant brings unique experience with the function of membrane proteins, including assay development, preparation methods, or studies with either purified proteins and living organisms. This emphasis on merging the production of membrane proteins for structure determination with the power of functional characterizations is the central philosophy of our Center. The TMPC has a primary goal of determining a founding structure for each of the unique target classes elaborated in this proposal. Our second goal is to establish an efficient membrane protein production pipeline so that increases in throughput may be progressively obtained. The TMPC expects to improve its ability to create protein variants, to refine screening based on functional and biophysical characterizations, and to improve sorting between multiple expressions pathways to find the best way produce a protein of interest. Emphasis on small-scale purification screening and further integration of automation into our efforts will increase efficiency. Expanded options for crystallization screening, access to synchrotrons, and improvements in software used to solve structures will also contribute to the increased throughput necessary to achieve PSI:Biology goals.