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，并利用多蛋白聚合酶复合体（PX）进行RNA复制和转录，这一过程对病毒的传染性、存活和繁殖至关重要。在含有双链RNA （dsRNA）基因组的囊病毒科（囊病毒）噬菌体中，PX是一个四蛋白复合物，包括一个RNA导向的RNA聚合酶（P2），该酶与蛋白质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下，对PX蛋白在空间和时间上的功能相互作用的完整理解不仅对囊病毒特别重要，而且对一般的dsRNA病毒也很重要。目前的项目将侧重于阐明涉及两种PX蛋白的结构/功能/动力学相关性，聚合酶P2形成PX的中心机制，执行转录和复制功能，以及调节基因组包装并帮助维持转录保原性的必需蛋白P7。纽约城市学院（CCNY）是一所主要为少数族裔服务的大学，在过去十年中，非裔美国学生注册本科学位课程的人数显著下降。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相应的人口增长。PI计划通过三层方法提高CCNY理科少数族裔的入学、留校和毕业水平：(1)招生：通过教师培训和PI实验室对少数有前途的学生进行研究指导，专门针对曼哈顿上城和布朗克斯以少数族裔学生为主的理科高中；(2)留用：通过城市学院职业准备学院（CCAPP）积极指导预科专业学生；(3)本科生研究：让本科生参与研究项目的特定部分，为他们提供在纽约城市大学系统中非常独特的体验，将两种前沿生物物理技术核磁共振和x射线晶体学相结合，以互补的方式阐明生物分子功能的结构和动态决定因素。