INVESTIGATIONS OF MACROMOLECULAR STRUCTURES AND DYNAMICS IN SOLUTION BY NMR

通过核磁共振研究溶液中的大分子结构和动力学

• 批准号: 5201953
• 负责人: A M GRONENBORN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5201953
• 关键词: DNA binding protein; bacterial proteins; cytokine; cytokine receptors; immunoglobulin G; interleukin 8; method development; molecular dynamics; nuclear magnetic resonance spectroscopy; protein folding; protein structure function; solutions; structural biology; thioredoxin; trypsin inhibitors

The objective of the overall research in this laboratory is centered on achieving as complete a description as possible for the structures of peptides, proteins, nucleic acids and their complexes in solution, principally by NMR spectroscopy. At present particular emphasis is being placed on developing approaches which allow the investigation of larger and complex systems as well as increase the precision with which these solution structures can be obtained, studies aimed at correlating structure and function, and experiments aimed at investigating protein folding. Structures for several proteins have been determined and analyzed. These include the oligomerization domain of p53, a complex of human thioredoxin with its target site from the transcription actor NFkB, the DNA binding domain of Mu transposase, the DNA binding domain of HIV-1 integrase, and the specific complex of human SRY (the male sex determining factor) with DNA. The latter provides the molecular basis for understanding mutations in SRY that lead to 46X,Y sex reversal. Studies on protein hydration have revealed the presence of conformationally disordered water within a large l00-l20_3 internal hydrophobic cavity of interleukin-1b. In addition, work on the unfolded state of Streptococcal Protein G is continuing and the structure and dynamics of the unfolded State have been characterized by NMR.

本实验室的总体研究目标集中在 尽可能完整地描述结构， 溶液中的肽、蛋白质、核酸及其复合物， 主要通过NMR光谱法。目前特别强调的是， 发展的方法，使调查更大的 和复杂的系统，以及提高精度，这些 可以获得溶液结构，研究旨在关联 结构和功能，以及旨在研究蛋白质的实验 折页. 已经确定和分析了几种蛋白质的结构。这些 包括p53的寡聚化结构域，p53是人硫氧还蛋白的复合物， 其靶位点来自转录因子NF κ B，DNA结合 Mu转座酶的DNA结合结构域，HIV-1整合酶的DNA结合结构域，和 人类SRY（男性性别决定因子）与 DNA. 后者为理解突变提供了分子基础 在SRY中导致46 X，Y性逆转。对蛋白质水合作用的研究 揭示了构象无序水的存在下， l00-l20_3白细胞介素-1b的内部疏水腔。 此外，对链球菌蛋白G的未折叠状态的研究是 继续和结构和动态展开的国家一直是 通过NMR表征。