调节 IL-10 作用的蛋白质的结构研究-猫眼课题宝

调节 IL-10 作用的蛋白质的结构研究

批准号：

8054785

负责人：

MARK R WALTER

金额：

$34.85万

依托单位：

UNIVERSITY OF ALABAMA AT BIRMINGHAM

依托单位国家：

美国

项目类别：

财政年份：

2001

资助国家：

美国

项目状态：

已结题

起止时间：

2001-01-01 至 2013-04-30

来源：

https://reporter.nih.gov/project-details/8054785

关键词：

Affinity Autoimmune Diseases B lymphoid malignancy B-Lymphocytes Binding Binding Sites Biological Biology Cell Surface Receptors Cell surface Cellular Structures Complement Complex Computer Simulation Congenital Abnormality Crystallography Cytomegalovirus Cytomegalovirus Infections Data Employee Strikes Exhibits Family Fluorescence Resonance Energy Transfer Funding Genome Goals Growth Factor Homologous Gene Human Human Herpesvirus 4 IL10RB gene Immune response Infection Inflammatory Response Interferons Interleukin-10 Kinetics Measurable Measures Mediating Methods NMR Spectroscopy Property Protein Dynamics Proteins Research Personnel Shapes Signal Transduction Site-Directed Mutagenesis Solutions Structural Models Structure Surface Plasmon Resonance System Techniques Therapeutic Viral Virus Virus Diseases X ray diffraction analysis X-Ray Crystallography autocrine base cell type cytokine defined contribution design improved interleukin 20 interleukin-22 metaplastic cell transformation mutant programs receptor receptor binding response three-dimensional modeling

项目摘要

项目成果

MARK R WALTER的其他基金

相似基金

相关文献

中文摘要

翻译

点击翻译按钮获取中文摘要

英文摘要

DESCRIPTION (provided by applicant): IL-10 is a multifunctional cytokine that regulates complex immune responses. Its normal function is to protect the host from uncontrolled inflammatory responses. However, IL-10 has also been implicated as an autocrine growth factor in several B-cell malignancies and stimulates B-cell mediated autoimmune disease. The normal and pathological functions of IL-10 are initiated by IL-10 receptor engagement and assembly into a signaling competent IL-10/IL-10R1/IL-10R2 complex. In addition to cellular IL-10 (clL-10), Epstein Barr virus (EBV) and cytomegalovirus (CMV) harbor viral IL-10 mimics (ebvlL-10 and cmvlL-10) in their genomes that activate the IL-10 signaling complex, resulting in overlapping and distinct biological properties. In the past funding period, we determined crystal structures of clL-10, cmvlL-10, and ebvlL-10 bound to the high affinity IL-10R1 chain. In this proposal we will use surface plasmon resonance, site-directed mutagenesis, NMR spectroscopy, X-ray crystallography, and FRET methods to study cellular and viral IL-10 receptor interactions. These studies will be complemented by the analysis of the cellular IL-10 homologs IL- 22 and IL-20. The long term goal of this proposal is to derive a quantitative structural/computational model of IL-10 family signaling that might explain how cellular and viral IL-10s shape immune responses and allow the rational design of cytokine therapeutics.

期刊论文(22)

专著(0)

科研奖励(0)

会议论文