STRUCTURAL STUDIES OF PROTEIN RECOGNITION

蛋白质识别的结构研究

• 批准号: 3877930
• 负责人: CHRISTIN FREDERICK
• 金额: --
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 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/3877930
• 关键词: DNA; DNA binding protein; Escherichia coli; X ray spectrometry; aminoacid tRNA ligase; antineoplastics; arsenic; bacterial proteins; bacterial virus; computer graphics /printing; conformation; crystallization; drug metabolism; enzyme structure; enzyme substrate complex; genetic manipulation; genetic operator element; histones; immunoglobulin structure; immunoglobulins; monoclonal antibody; nonhistone nucleoprotein; nucleic acid chemical synthesis; oligonucleotides; peptide chemical synthesis; protein engineering; protein structure function; synthetic peptide; transfer RNA; virus protein

The recognition and subsequent interactions between a protein and other molecules play essential roles in many fundamental biological processes. The overall objective of this project is to understand the molecular basis of how proteins recognize other molecules, including small molecule ligands as well as macromolecules such as nucleic acids and proteins, using single crystal x-ray diffraction studies. The rationale of the work here is that proteins may possess certain characteristic folding "motifs" for their substrate binding functions. Specifically, we propose to crystallize and determine the three dimensional structure of several proteins systems. These include 1) proteins that interact with DNA: E. coli Hu protein, Ike and fd gene 5 protein and E. coli Rep enzyme and their complexes with DNA oligonucleotides; 2) Aminoacyl tRNA synthetase fragments and their complexes with tRNA; 3) Fab fragments of antiarsonate immunoglobulins; 4) Synthetic peptides possessing DNA binding activity. We hope to crystallize these proteins with and without their respective substrates so that we can visualize the structure of the protein before and after complex formation. Detailed knowledge of the protein structure will allow us to assess the conformational changes in the protein molecule and to predict ways of altering existing proteins or designing new proteins of various functions. The proposed studies in this project involve collaboration with other principal investigators in the program project. By combining the knowledge of recombinant DNA methodology, monoclonal antibody technology, nucleotide and peptide chemistry and x-ray crystallography within the program project, we hope ultimately to achieve the long range goal of understanding the structure, interactions and function of proteins and of designing new proteins of improved or desired functions.

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