Center on Membrane Protein Production and Analysis (COMPPAA)

 描述（由申请人提供）：膜中的蛋白质提供细胞内膜界定的细胞器和细胞本身与其外部环境通信的门户。这些基本性质使膜蛋白成为生物化学和细胞生物学中的关键组分。许多膜蛋白参与疾病的过程，并且它们是超过40%的FDA批准的药物的分子靶点。原子水平的结构为生化理解和药物发现提供了信息。然而，尽管膜蛋白占所有生命中所有蛋白质的20-30%，但膜蛋白的结果仅占蛋白质数据库中原子结构的1.6%。在很大程度上，这种结构代表性不足的出现是因为在生产和分析膜蛋白的结构和功能的挑战。需要新技术来应对这些挑战。我们建议将膜蛋白生产和分析中心（COMPPAA，或简称COMPPSAND）发展为生物医学技术研究资源（BTRR），用于生产和研究与生物学和医学相关的膜蛋白。我们将建立在现有的设施和人才在纽约结构生物学中心（NYSBC），其中包括通过X射线晶体学，冷冻电子显微镜（cryo-EM）和NMR光谱结构测定的能力，以及高通量表达测试和洗涤剂筛选膜蛋白的设施。COMPPER将有九个组成部分，包括四个技术研究和开发（TR&D）项目，这些项目将由驱动生物医学项目（DBP）组成部分驱动，该组成部分将包括15个选定的DBP，作为TR&D开发的试验台。TR&D1将开发有效生产重组膜蛋白的技术。TR&D2将开发用于结构分析的膜蛋白样品优化技术。TR&D3将开发用于功能分析的通用检测试剂盒

 DESCRIPTION (provided by applicant): Proteins in membranes provide the portals through which membrane-delimited organelles within cells and cells themselves communicate with their external environments. These essential properties make membrane proteins crucial components in biochemistry and in cell biology. Many membrane proteins are involved in processes of disease, and they are the molecular targets of over 40% of all FDA-approved drugs. Atomic level structure informs both biochemical understanding and drug discovery. Yet, whereas membrane proteins constitute 20-30% of all proteins in all of life, results from membrane proteins comprise only 1.6% of atomic structures in the Protein Data Bank. To a large extent, this structural under-representation arises because of the challenges in producing and analyzing membrane protein structure and function. New technology is needed to address these challenges. We propose to develop the Center on Membrane Protein Production and Analysis (COMPPAA, or COMPPÅ for short) as a Biomedical Technology Research Resource (BTRR) for the production and study of membrane proteins of relevance to biology and medicine. We will build on existing facilities and talents at the New York Structural Biology Center (NYSBC), which include capabilities for structure determination by x-ray crystallography, cryo-electron microscopy (cryo-EM) and NMR spectroscopy as well as a facility for high-throughput expression testing and detergent screening for membrane proteins. COMPPÅ will have nine components including four Technology Research and Development (TR&D) projects which will be driven by Driving Biomedical Project (DBP) component that will comprise fifteen selected DBPs to serve as test beds for the TR&D development. TR&D1 will develop technology for the efficient production of recombinant membrane proteins. TR&D2 will develop technology for the optimization of membrane protein samples for structural analysis. TR&D3 will develop generic assays for functional analy