Chaperone-Assisted RNA Crystallography-Equipment Supplement

分子伴侣辅助 RNA 晶体学设备补充品

基本信息

  • 批准号:
    9895189
  • 负责人:
  • 金额:
    $ 8.6万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-04-01 至 2021-11-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY FROM PARENT AWARD Biological systems possess a highly complex and dynamic cellular RNA population, collectively known as the transcriptome. Many RNAs fold into complex three-dimensional structures, both intrinsically and as ribonucleoprotein (RNP) complexes, and play fundamental roles in nearly every aspect of gene expression. Understanding cell biology, health, and disease requires knowledge of how RNA structure mediates biological function. X-ray crystallography provides a powerful method for structure determination, but RNA crystallization represents a major bottleneck in the process, reflecting in part the limited surface chemistry for mediating lattice interactions and repulsion among the phosphates. Considering the rapid pace of new RNA discovery, there remains an acute need to develop methods to facilitate RNA structure acquisition. For difficult protein targets, antibody fragments (Fab or scFv) have served as effective chaperones for crystallization, and we hypothesized that the large size, conformational properties and surface chemistry of Fabs will facilitate RNA crystallization as well. Using phage-display library selections we demonstrated that Fabs can bind RNA with high affinity and specificity, mediate the majority of lattice interactions in Fab-RNA co-crystals, and provide a molecular replacement model for solving the structures. The long-term goal of this project is to facilitate resolution of the RNA crystallization bottleneck through development of a high-throughput pipeline for antibody production against RNA. The objective of this application is to enable facile access to RNA- binding Fabs and pursue them as reagents for RNA and RNP crystallization and structure determination. To attain this objective we will (a) improve Fab libraries using phage display and molecular evolution approaches to identify amino acid types that tailor complementary determining regions (CDRs) for RNA binding, (b) develop general use crystallization modules with surface and conformational properties adjusted to facilitate crystallization, and (c) use these techniques to create and use Fab complexes of RNA and RNP targets for crystallization and structure determination. Completion of the research will allow facile access to RNA binding Fabs, provide structural biologists with a suite of portable modules for generalized use in RNA/RNP crystallization, and provide important new structural knowledge for understanding biological function.
帕萨特奖项目总结 生物系统拥有高度复杂和动态的细胞RNA群体,统称为 转录组许多RNA折叠成复杂的三维结构,无论是内在的还是作为 核糖核蛋白(RNP)复合物,并在基因表达的几乎每个方面发挥重要作用。 了解细胞生物学,健康和疾病需要了解RNA结构如何介导生物学, 功能X射线晶体学提供了一种强有力的结构测定方法,但RNA 结晶代表了该过程中的主要瓶颈,部分反映了用于制备纳米颗粒的有限的表面化学性质。 介导磷酸盐之间的晶格相互作用和排斥。考虑到新RNA的快速发展 然而,尽管RNA结构的发现已经被证实,但仍然迫切需要开发促进RNA结构获取的方法。对困难 蛋白质靶标,抗体片段(Fab或scFv)已经充当用于结晶的有效伴侣,并且 我们假设Fab的大尺寸、构象特性和表面化学将促进 RNA结晶也是如此。使用噬菌体展示文库选择,我们证明Fab可以结合RNA, 具有高亲和力和特异性,介导Fab-RNA共晶体中的大多数晶格相互作用, 为求解结构提供了分子置换模型。该项目的长期目标是 通过开发高通量流水线促进解决RNA结晶瓶颈 用于产生针对RNA的抗体。本申请的目的是使人们能够方便地获取RNA- 结合Fab,并将它们用作RNA和RNP结晶和结构测定的试剂。到 为了达到这一目标,我们将(a)使用噬菌体展示和分子进化方法改进Fab文库 鉴定为RNA结合定制互补决定区(CDR)的氨基酸类型,(B) 开发通用的结晶模块,其表面和构象特性经过调整, (c)使用这些技术来产生和使用RNA和RNP靶标的Fab复合物, 结晶和结构测定。这项研究的完成将使RNA结合变得容易 Fabs为结构生物学家提供了一套便携式模块,用于RNA/RNP的广泛使用 结晶,并为理解生物功能提供重要的新结构知识。

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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Joseph Anthony Piccirilli其他文献

Joseph Anthony Piccirilli的其他文献

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{{ truncateString('Joseph Anthony Piccirilli', 18)}}的其他基金

Structure and Function of Non-Coding RNA
非编码RNA的结构和功能
  • 批准号:
    10623993
  • 财政年份:
    2023
  • 资助金额:
    $ 8.6万
  • 项目类别:
The VS Ribozyme: Catalytic Mechanism, Transition State Structure, and Evolution
VS 核酶:催化机制、过渡态结构和进化
  • 批准号:
    10305610
  • 财政年份:
    2019
  • 资助金额:
    $ 8.6万
  • 项目类别:
The VS Ribozyme: Catalytic Mechanism, Transition State Structure, and Evolution
VS 核酶:催化机制、过渡态结构和进化
  • 批准号:
    10582360
  • 财政年份:
    2019
  • 资助金额:
    $ 8.6万
  • 项目类别:
The VS Ribozyme: Catalytic Mechanism, Transition State Structure, and Evolution
VS 核酶:催化机制、过渡态结构和进化
  • 批准号:
    10061618
  • 财政年份:
    2019
  • 资助金额:
    $ 8.6万
  • 项目类别:
CHAPERONE-ASSISTED RNA CRYSTALLOGRAPHY - Resubmission 01
伴侣辅助 RNA 晶体学 - 重新提交 01
  • 批准号:
    8506004
  • 财政年份:
    2013
  • 资助金额:
    $ 8.6万
  • 项目类别:
Chaperone-Assisted RNA Crystallography
分子伴侣辅助 RNA 晶体学
  • 批准号:
    10058842
  • 财政年份:
    2013
  • 资助金额:
    $ 8.6万
  • 项目类别:
CHAPERONE-ASSISTED RNA CRYSTALLOGRAPHY - Resubmission 01
伴侣辅助 RNA 晶体学 - 重新提交 01
  • 批准号:
    9037690
  • 财政年份:
    2013
  • 资助金额:
    $ 8.6万
  • 项目类别:
CHAPERONE-ASSISTED RNA CRYSTALLOGRAPHY - Resubmission 01
伴侣辅助 RNA 晶体学 - 重新提交 01
  • 批准号:
    8643797
  • 财政年份:
    2013
  • 资助金额:
    $ 8.6万
  • 项目类别:
The Catalytic Mechanism of Nuclear Premessenger RNA Splicing by the Spliceosome
剪接体对核前信使RNA剪接的催化机制
  • 批准号:
    8788330
  • 财政年份:
    2010
  • 资助金额:
    $ 8.6万
  • 项目类别:
Investigating the Catalytic Mechanism of the HDV Ribozyme
HDV 核酶催化机制的研究
  • 批准号:
    8465171
  • 财政年份:
    2010
  • 资助金额:
    $ 8.6万
  • 项目类别:

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