Integrated Center for Structure and Function Innovation

结构与功能创新综合中心

• 批准号: 7277885
• 负责人: THOMAS C. TERWILLIGER
• 金额: $ 33.73万
• 依托单位: LOS ALAMOS NAT SECTY-LOS ALAMOS NAT LAB
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7277885
• 关键词: biomedical resource; cooperative study; functional /structural genomics; protein structure function; proteomics

DESCRIPTION (provided by applicant): The Integrated Center for Structure and Function Innovation (ISFI) will be a PSI-2 Specialized Center developing and applying a set of synergistic technologies organized to overcome recognized bottlenecks in structure determination at the key steps of production of soluble protein and protein crystallization. The development of these technologies will be embedded in an integrated pipeline for protein structure determination and analysis of function, and the technologies will be applied to difficult proteins and protein complexes from large sequence families, emphasizing proteins with high biological significance. The increased success rates made possible by our technologies will be critical for obtaining structures of proteins and protein complexes of high functional value, both for the PSI and for structural biology as a whole. The increased success rates will lead as well to substantial cost reductions in structure determination. Our application of our methodologies as part of this project will enhance the understanding of protein function and protein-protein interactions relevant to human health. The core technologies to be developed in the ISFI are: (1) systematic construction of protein binding partners for chaperone-assisted crystallography, (2) engineering proteins for crystallization by surface mutagenesis and addition of fusion proteins, (3) directed evolution of proteins for solubility and trapping of protein partners required for folding using one member attached to a reporter protein as a bait, (4) identification of protein partners required for proper folding using informatics approaches confirmed by experiments, and (5) systematic combinatorial crystallization screening and optimization. These technologies will be used to address five major bottlenecks in the structural genomics pipeline: (a) soluble expression, (b) small protein complexes, (c) crystallizability, (d) soluble domains of membrane proteins, and (e) eukaryotic protein structure determination. The technologies will be developed through highly integrated collaborations among 6 institutions. Technologies and results will be made available to other Centers and the broader structural biology community through workshops, publications, personnel exchanges, and the web.

描述（由申请人提供）：结构和功能创新集成中心（ISFI）将是一个PSI-2专业中心开发和应用一组协同技术，以在生产可溶性蛋白质和蛋白质结晶的关键步骤中在结构确定中组织出来，以克服公认的瓶颈。 这些技术的开发将嵌入蛋白质结构的确定和功能分析的集成管道中，并且该技术将应用于大序列家族的困难蛋白质和蛋白质复合物，强调具有高生物学意义的蛋白质。 我们的技术使成功率的提高对于获得PSI和整个结构生物学的蛋白质和蛋白质复合物的结构至关重要。成功率的提高将导致结构确定的大量成本降低。 我们将方法作为该项目的一部分的应用将增强对与人类健康相关的蛋白质功能和蛋白质蛋白质相互作用的理解。 ISFI中要开发的核心技术是：（1）蛋白质结合伴侣的系统构建用于伴侣辅助辅助晶体学的蛋白质结合伙伴，（2）通过表面诱变和融合蛋白的添加来结晶的工程蛋白质，（3）（3）蛋白质的定向进化，用于蛋白质的蛋白质和蛋白质属性（4），以替代蛋白质的属性（4），以替代蛋白质构图（4）构成（4）构成（4）构成（4）属性（4）蛋白质的依从性（4）蛋白质的依从性（4）属性（4）成员（4）。使用实验确认的信息方法进行适当折叠所需的蛋白质伴侣，以及（5）系统的组合结晶筛选和优化。 这些技术将用于解决结构基因组学管道中的五个主要瓶颈：（a）可溶性表达，（b）小蛋白质复合物，（c）结晶性，（d）膜蛋白的可溶性结构域和（e）真核蛋白质结构的确定。 这些技术将通过6个机构之间的高度综合合作开发。技术和结果将通过研讨会，出版物，人事交流和网络提供给其他中心和更广泛的结构生物学社区。