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: 3776284
• 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/3776284
• 关键词: DNA binding protein; bacterial proteins; biophysics; immunoglobulin G; interleukin 1; interleukin 4; interleukin 8; method development; molecular dynamics; nuclear magnetic resonance spectroscopy; protein folding; protein structure; protein structure function; solutions; transcription factor

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 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 cytokine interleukin-4, and the complex of the DNA binding domain of the erythroid transcription factor GATA-1 with its specific DNA target site. These studies have exploited many novel 3D and 4D heteronuclear NMR experiments to dramatically increase spectral resolution and thereby resolve assignment ambiguities in larger proteins. The dynamics of the cytokine interleukin-8 have been explored. The contact surface of the IgG binding domain of Streptococcal G complexed with a human IgGFc has been identified. Finally, the folding pathway and kinetics of the all beta- sheet protein interleukin-1beta have been investigated.

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， 复杂的系统，以及提高精度，这些解决方案 可以获得结构，旨在将结构和 功能，以及旨在研究蛋白质折叠的实验。 已经确定和分析了几种蛋白质的结构。 这些 包括细胞因子白细胞介素-4和DNA结合复合物， 红系转录因子加塔-1的结构域及其特异性DNA 目标部位。这些研究开发了许多新颖的3D和4D 异相NMR实验，以显着提高光谱分辨率 从而解决较大蛋白质中的分配模糊性。动力学 细胞因子白细胞介素-8已经被探索。的接触表面 与人IgGFc复合的链球菌G的IgG结合结构域具有 被识别。最后，全β- 已经研究了折叠蛋白白细胞介素-1 β。