Small Angle X-ray Scattering Instrument

描述（申请人提供）：申请的仪器是小角度x射线散射（SAXS）仪器。SAXS仪器将用于研究生物大分子及其复合物在溶液中的结构。SAXS提供有关大分子形状、折叠、展开、聚集、扩展构象、灵活连接域、构象变化和溶液中组装状态的低（10-20）分辨率信息。SAXS数据可以为生物分子功能提供新的见解，否则无法通过其他手段获得。例如，在许多情况下，单个蛋白质结构域结构是已知的，但整个蛋白质的整体组装状态以及它如何响应其他分子是未知的，但可以通过SAXS精确推断。SAXS的优点是它是一种基于溶液的方法，因此分子不受晶格的限制，也没有核磁共振的尺寸限制。此外，SAXS所需的材料比核磁共振或x射线晶体学少得多。该仪器将通过提供对分子功能很重要的溶液中的分子形状、结构域取向和构象变化的信息，影响17个美国国立卫生研究院资助的研究项目。该仪器所服务的NIH资助项目在以下领域与人类健康有直接关系：与甜味受体的配体结合；前信使RNA剪接；ATP结合诱导病原菌菌毛中的亚基运动；脂肪酸生物合成；蛋白质介导的铁硫团簇组装；维生素D受体在医学上相关的维生素D3类似物存在下的相互作用；心脏病毒前导蛋白与RAN GTPase的相互作用；HIV-1移码位点RNA结构；理解RNA折叠途径作为细胞离子和渗透物的功能；单链结合蛋白（SSB）在基因组维持中的作用伴侣蛋白Hsp70；组蛋白修饰酶与其调控蛋白的相互作用，以及参与纤维连接蛋白和血小板功能的基质蛋白。此外，SAXS数据可以直接用于核磁共振结构测定，以提高核磁共振结构的质量（NMR-SAXS），这是一项新兴技术，扩展了核磁共振的前沿，以确定更大、更精确的结构。

DESCRIPTION (provided by applicant): The instrument requested is a small angle X-ray scattering (SAXS) instrument. The SAXS instrument will be used for investigating the structures of biological macromolecules and their complexes in solution. SAXS provides low (10-20 ¿) resolution information about macromolecular shape, folding, unfolding, aggregation, extended conformations, flexibly linked domains, conformational changes, and assembly state in solution. SAXS data can provide novel insights into biomolecular function that would otherwise not be attainable by other means. For example, there are many cases where individual protein domain structures are known, but the overall assembled state of the entire protein, and how it responds to other molecules, is not known but can be accurately deduced by SAXS. The advantages of SAXS are that it is a solution-based method, so the molecules are not constrained by a crystalline lattice, and there is no size limitation as is the case with NMR. Additionally, SAXS requires much less material than either NMR or X-ray crystallography. The instrument will impact 17 NIH-funded research projects by providing information about molecular shape, domain orientations and conformational changes in solution that are important for molecular function. The NIH funded projects served by the instrument have direct relationship to human health in the areas of: ligand binding to the sweet taste receptor; pre- messenger RNA splicing; binding of ATP to induce subunit movement in the pili of pathogenic bacteria; fatty acid biosynthesis; protein mediated iron-sulfur cluster assembly; interaction of the vitamin D receptor in the presence of medically relevant vitamin D3 analogs; interaction of the cardioviral Leader protein and the RAN GTPase; the HIV-1 frameshift site RNA structure; understanding RNA folding pathways as a function of cellular ions and osmolytes; role of single stranded binding (SSB) protein in genome maintenance; the chaperone Hsp70; the interaction of histone modifying enzymes with their regulatory proteins, and matrix proteins involved in fibronectin and platelet function. Additionally, SAXS data can be used directly in NMR structure determination to improve the quality of NMR structures (NMR-SAXS), which is an emergent technology that extends the frontiers of NMR for determining larger and more accurate structures. ) PUBLIC HEALTH RELEVANCE: The requested instrument will serve 17 NIH funded projects that have direct relationship to human health in the areas of: ligand binding to the sweet taste receptor; pre-messenger RNA splicing; binding of ATP to induce subunit movement in the pili of pathogenic bacteria; fatty acid biosynthesis; protein mediated iron-sulfur cluster assembly; interaction of the vitamin D receptor in the presence of medically relevant vitamin D3 analogs; interaction of the cardioviral Leader protein and the RAN GTPase; the HIV-1 frameshift site RNA structure; understanding RNA folding pathways as a function of cellular ions and osmolytes; role of single stranded binding (SSB) protein in genome maintenance; the chaperone Hsp70; the interaction of histone modifying enzymes with their regulatory proteins, and matrix proteins involved in fibronectin and platelet function. Additionally, SAXS data will be used directly in NMR structure determination in order to extend the frontiers of NMR for determining larger and more accurate structures of biologically important macromolecules.