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Characterizing proteasome-substrate interactions by mass spectrometry proteomics

通过质谱蛋白质组学表征蛋白酶体-底物相互作用

基本信息

批准号：
10377447
负责人：
DAVID E. CLEMMER
金额：
$ 34.15万
依托单位：
TRUSTEES OF INDIANA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10377447
关键词：
Affinity Analytical Chemistry Attenuated Binding Biochemical Biochemistry Bioinformatics Biological Biological Assay Cell physiology Cells Cellular biology Chemicals Collaborations Complex Crosslinker Data Data Analyses Development Discipline Disease Resistance Elements Genetic Geometry Hematologic Neoplasms Immune response In Vitro Indiana Ions Kinetics Ligands Maintenance Mass Spectrum Analysis Methodology Methods Modification Molecular Molecular Biology Mutagenesis Neurodegenerative Disorders Peptides Physiological Polyubiquitin Process Proteasome Binding Proteasome Inhibitor Protein Engineering Proteins Proteome Proteomics Quality Control Reporting Research Research Personnel Role Signal Transduction Site Specificity Structure Substrate Interaction System Testing Texas Ubiquitin Ubiquitination Universities Yeasts austin crosslink data acquisition defined contribution detection sensitivity experience experimental study genetic regulatory protein healthy aging improved instrumentation multicatalytic endopeptidase complex novel polypeptide protein degradation proteostasis purge receptor therapeutic target yeast genetics

项目摘要

PROJECT SUMMARY This application features a close collaboration between bioanalytical (Dr. Reilly, Indiana University) and bio- chemistry (Dr. Matouschek, University of Texas, Austin) research groups aimed at improving our understanding of the ubiquitin-proteasome protein degradation system. The investigators contribute complementary expertise and experience in a variety of disciplines ranging from proteomics, protein bioinformatics, analytical chemistry and instrumentation, to biochemistry, molecular biology and cell biology. At Indiana University, cross-linking mass spectrometry will be combined with biochemical and genetic assays to characterize the interaction between the proteasome and its substrates to provide candidates for novel substrate receptors on the proteasome. At The University of Texas at Austin, the biological relevance of candidates will then be tested in biochemical pro- teasome assays and genetic yeast experiments. These assays will define the contribution of newly identified components to substrate recognition and degradation by the proteasome and elucidate the molecular and struc- tural origin of substrate selection and specificity. Overall, we believe that this proposal will result in significant advances in cross-linking methodology and in our understanding of how the proteasome recognizes and digests substrates.

项目摘要该应用程序的特点是生物分析（Reilly博士，印第安纳州大学）和生物化学（Matouschek博士，得克萨斯大学，奥斯汀）的研究小组，旨在提高我们的理解泛素-蛋白酶体蛋白质降解系统。调查人员提供补充性专门知识在蛋白质组学，蛋白质生物信息学，分析化学等多个学科的经验和仪器，到生物化学，分子生物学和细胞生物学。在印第安纳州大学，质谱分析将与生物化学和遗传分析相结合，以表征蛋白酶体及其底物，以提供蛋白酶体上新底物受体的候选物。在得克萨斯大学奥斯汀分校的生物学相关性考生随后将进行生化亲测， teasome分析和遗传酵母实验。这些试验将确定新鉴定的蛋白酶体对底物的识别和降解，并阐明其分子和结构。底物选择和特异性的自然起源。总的来说，我们认为，这一建议将导致重大进展的交联方法和我们的了解蛋白酶体如何识别和消化底物。