Structure/Dynamics/Function Correlations in the Cystoviral Polymerase Complex

囊病毒聚合酶复合物的结构/动力学/功能相关性

• 批准号: 0843141
• 负责人: Ranajeet Ghose
• 金额: $ 99.2万
• 依托单位: CUNY City College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0843141&HistoricalAwards=false
• 关键词: Structure; Dynamics; Function; Correlations; Cystoviral

Many viruses contain RNA genomes and utilize a multi-protein polymerase complex (PX) for RNA replication and transcription, processes that are central to viral infectivity, survival and propagation. In bacteriophages of the family cystoviridae (cystoviruses) that contain a double stranded RNA (dsRNA) genome, the PX is a four-protein complex that includes an RNA-directed RNA polymerase (P2) that replicates and transcribes viral RNA (vRNA) in concert with proteins P1, P4 and P7. A complete understanding of the functional interactions of the PX proteins in spatial and temporal terms at atomic or near-atomic resolution is important not only in the context of cystoviruses in particular but for dsRNA viruses in general. The present project will focus on elucidating structure/function/dynamics correlations involving two of these PX proteins, the polymerase P2 that forms the central machinery of the PX, performing the transcription and replication functions, and the essential protein P7 that regulates genome packaging and helps in maintaining transcriptional fidelity.The City College of New York (CCNY), a primarily minority serving institution, has registered a significant drop in the number of African-American students enrolling in undergraduate degree programs over the last decade. The level of enrollment of Hispanic students has also not kept up with a corresponding population increase in the five boroughs of New York City over the same period. The PI intends to raise the level of enrollment, retention and graduation of these minority populations in the science disciplines at CCNY using a three-tier approach: (1) Enrollment: specifically targeting high-schools specializing in the sciences in upper Manhattan and the Bronx with predominantly minority students, through teacher training and by research mentoring of a small number of promising students in the PI's laboratory; (2) Retention: active mentoring of pre-science majors through the City College Academy for Professional Preparation (CCAPP); and (3) Undergraduate research: involving undergraduate students in specific parts of the research project, providing them an experience rather unique in the City University of New York system of incorporating two cutting edge biophysical techniques NMR and X-Ray crystallography in a complementary fashion to elucidate the structural and dynamic determinants of biomolecular function.

许多病毒含有RNA基因组，并利用多蛋白质聚合酶复合物（PX）进行RNA复制和转录，这对于病毒感染，存活和传播至关重要。在包含双链RNA（dsRNA）基因组的cystoviridae（囊肿病毒）的拟噬菌噬细胞中，PX是一种四蛋白蛋白复合物，其中包括RNA指导的RNA聚合酶（P2），可复制并与蛋白质P1，P1，P4和P7一起复制和转录病毒RNA（VRNA）。在原子或近原子分辨率上，对PX蛋白在空间和时间术语中的功能相互作用的完全理解不仅在脊髓病毒的背景下，而且对于通常的DSRNA病毒而言很重要。 The present project will focus on elucidating structure/function/dynamics correlations involving two of these PX proteins, the polymerase P2 that forms the central machinery of the PX, performing the transcription and replication functions, and the essential protein P7 that regulates genome packaging and helps in maintaining transcriptional fidelity.The City College of New York (CCNY), a primarily minority serving institution, has registered a significant drop in the在过去十年中，非裔美国人的学生参加了大学学位课程。在同一时期，西班牙裔学生的入学水平也没有跟上纽约市五个行政区的相应人口增加。 PI打算使用三层方法提高这些少数人群在CCNY的科学学科的入学水平，保留和毕业水平：（1）入学率：专门针对高中生的高中生，专门针对上曼哈顿的科学，并通过教师培训，通过教师培训和少数培训，并通过研究培训，并通过少数培训训练，并通过少数培训来进行培训和小组培训。 （2）保留：通过城市学院专业准备学院（CCAPP）积极指导科学专业的专业； （3）本科研究：让本科生参与研究项目的特定部分，为它们提供了纽约市大学的体验，以互补的方式融合了两种尖端生物物理技术NMR和X射线晶体学，以阐明生物分解功能的结构和动态决定性。