INCISIVE OF NUCLEIC ACID CONFORMATIONAL HETEROGENEITY: DNA BULGES

尖锐的核酸构象异质性：DNA 凸出

基本信息

批准号：
8170218
负责人：
Xuan-Zheng Peter Shi
金额：
$ 0.1万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2011-02-28
项目状态：
已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Using small-angle x-ray scattering interference between gold nanocrystal labels, Mathew-Fenn et al. have measured the end-to-end length for a series of DNA double helices in solution. This newly developed Au-SAXS-based x-ray ruler provides the distance probability distribution of an ensemble of molecules. Thus, this technique provides a unique and powerful probe of macromolecular conformational heterogeneity. To establish this ability of this x-ray ruler technique, we propose to study the conformational flexibility and heterogeneity in DNA helices with bulged nucleotides. A-bulges have been shown to bend DNA, giving a good starting point for these studies, but the degree of underlying conformational heterogeneity is unknown. We will compare the effect of A and U bulges of length 1-5 on DNA bending and heterogeneity. We are applying for rapid access because Dr. Mathew-Fenn, the originator of this technique, will leave Stanford in mid-April and we would like to carry out initial SAXS experiments before her departure. Mathew-Fenn et al. have measured the end-to-end length for a series of DNA double helices in solution. This newly developed Au-SAXS-based x-ray ruler provides the distance probability distribution of an ensemble of molecules. Thus, this technique provides a unique and powerful probe of macromolecular conformational heterogeneity. To establish this ability of this x-ray ruler technique, we propose to study the conformational flexibility and heterogeneity in DNA helices with bulged nucleotides. A-bulges have been shown to bend DNA, giving a good starting point for these studies, but the degree of underlying conformational heterogeneity is unknown. We will compare the effect of A and U bulges of length 1-5 on DNA bending and heterogeneity.

该子项目是利用该技术的众多研究子项目之一资源由 NIH/NCRR 资助的中心拨款提供。子项目和研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金，因此可以在其他 CRISP 条目中表示。列出的机构是对于中心来说，它不一定是研究者的机构。 Mathew-Fenn 等人利用金纳米晶体标记之间的小角度 X 射线散射干扰。测量了溶液中一系列 DNA 双螺旋的端到端长度。这种新开发的基于 Au-SAXS 的 X 射线标尺提供了分子集合的距离概率分布。因此，该技术提供了大分子构象异质性的独特且强大的探针。为了建立这种 X 射线标尺技术的能力，我们建议研究具有凸出核苷酸的 DNA 螺旋的构象灵活性和异质性。 A-凸起已被证明可以弯曲 DNA，为这些研究提供了一个良好的起点，但潜在的构象异质性程度尚不清楚。我们将比较长度为 1-5 的 A 和 U 凸起对 DNA 弯曲和异质性的影响。我们正在申请快速访问，因为这项技术的创始人 Mathew-Fenn 博士将于 4 月中旬离开斯坦福大学，我们希望在她离开之前进行初步的 SAXS 实验。马修-芬恩等人。测量了溶液中一系列 DNA 双螺旋的端到端长度。这种新开发的基于 Au-SAXS 的 X 射线标尺提供了分子集合的距离概率分布。因此，该技术提供了大分子构象异质性的独特且强大的探针。为了建立这种 X 射线标尺技术的能力，我们建议研究具有凸出核苷酸的 DNA 螺旋的构象灵活性和异质性。 A-凸起已被证明可以弯曲 DNA，为这些研究提供了一个良好的起点，但潜在的构象异质性程度尚不清楚。我们将比较长度为 1-5 的 A 和 U 凸起对 DNA 弯曲和异质性的影响。