TELOMERASE STRUCTURE AND FUNCTION

端粒酶结构和功能

• 批准号: 7598699
• 负责人: G VARANI
• 金额: $ 0.21万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598699
• 关键词: Apical; Binding; Biogenesis; Computer Retrieval of Information on Scientific Projects Database; Coupling; Data; Data Quality; Enzymes; Eukaryota; Eukaryotic Cell; Funding; Goals; Grant; Holoenzymes; Human; Institution; Methods; Nucleotides; Pliability; Protein Binding Domain; Proteins; RNA; RNA Processing; Research; Research Personnel; Residual state; Resolution; Resources; Ribonucleoproteins; Source; Structure; Telomerase; Telomerase RNA Component; United States National Institutes of Health; Vertebrates; Work; base; chromosome replication; telomere

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Telomerase is the ribonucleoprotein (RNP) enzyme responsible in most eukaryotes for the replication of the chromosome termini (telomeres). It is composed of a 400-nucleotide RNA and several proteins that associate with it and carry out the enzymatic activity and promote its cellular localization and assembly. There are at the moment only a few high-resolution structures from telomerase components. We are studying the structure of two critical domains of human telomerase RNA responsible respectively for RNA biogenesis and for recruitment of the catalytic activity to the holoenzyme. Four proteins of unknown structure bind to human telomerase RNA: in doing so, they stabilize the RNA and direct RNA processing. We aim to determine the structures of three such proteins (called Nop10, Nhp2 and Gar1) and of the RNA domain they associate with. NMR studies conducted in Seattle have provided us with very high quality data for all three proteins, for an RNA sub-domain (called CR7) that is essential for telomerase biogenesis and for the entire domain of 80 nucleotides responsible for RNP assembly. In vertebrates, the catalytic activity of telomerase associates with the RNA template by binding a domain of the RNA component of telomerase called CR4/CR5. The enzyme binds directly to two structures within this domain; the NMR work on the CR4/CR5 domain has progressed significantly: we are collecting residual dipolar coupling data to refine the structure of the apical part of the domain. Our goal is to dissect the structure and conformational flexibility of these domains and of the proteins that bind to them by combining well-established methods of NMR structure determination with new methods based on residual dipolar couplings.

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