Structural and Biochemical Studies of Crenarchael Viral Proteins

Crearchael 病毒蛋白的结构和生化研究

• 批准号: 0628732
• 负责人: Martin Lawrence
• 金额: $ 58.36万
• 依托单位: Montana State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0628732&HistoricalAwards=false
• 关键词: Structural; Biochemical; Studies; Crenarchael; Viral

Crenarchaeal viruses such as SSV and STIV exist in extreme thermal (175 to 200 degrees Fahrenheit) and acidic (1.0 pH 3.0) environments such as those found in Yellowstone National Park. While SSV and STIV are among the best characterized Crenarchaeal viruses, our understanding of these unique hyperthermophilic viruses is limited. For example, sequence analysis of the SSV and STIV genomes fails to identify homologues for the majority of the putative genes. Hence, most viral proteins have yet to be assigned any function, and the roles that these proteins play in the viral life cycles remains a mystery. This project uses structural biology and biochemistry to (i) investigate the functional roles of the SSV and STIV proteomes. The structures of these proteins will be determined using X-ray crystallography. In many cases, the similarity of a structure to those in the Protein Data Bank is expected to suggest a function for the viral protein. In addition, this project seeks to (ii) identify viral or host proteins, or DNA sequences, that interact with specific viral proteins to form higher order complexes. Identification of these interacting macromolecules will provide further functional insight. Together, these efforts will contribute to an increased understanding of the SSV and STIV life cycles at the molecular level and thus this project represents a significant step toward understanding the unique viruses that inhabit these extreme environments. In addition, these viruses are of great interest because they serve as model systems for understanding the biochemistry and molecular biology required for life at high temperatures. Through their interactions with host machinery, they provide entry points for the study of important biochemical events, thus opening windows onto the most fundamental processes of the still poorly understood Crenarchaeota. Historically, viruses have also been a source of novel enzymes for biotechnology, particularly enzymes involved in nucleic acid biosynthesis and modification. Thus, identification of thermostable enzymes from the Crenarchaeal viruses might have important applications in biotechnology. Finally, the insights to be gained from comparative investigation of viruses from all three domains of life will be helpful in providing a better understanding of viral genesis and evolution.Broader Impacts: Much of the ongoing work within the Thermal Biology Institute (TBI) at Montana State University is being communicated to the general public by TBI outreach programs. Work on hyperthermophilic viruses is one of the focal points within TBI and is thus a major focus of these outreach efforts. Partners in outreach include the National Park Service /Yellowstone National Park, and involve preparation and review of materials for public presentation within the Park. The Park System is increasingly aware, as is the general public, of the unique microbial organisms inhabiting these world famous thermal features, and is working to increase the educational signage within the park that describes these organisms. There is strong integration of the research with the educational goals of the PI, the Department, the University, and the NSF. Students at the high school, undergraduate, doctoral and post-doctoral levels will receive significant training in biochemistry, structural biology and thermal biology. The participation of under represented groups, particularly women and Native Americans is encouraged, and their participation is well documented.

像SSV和STIV这样的古细菌病毒存在于极端高温（175到200华氏度）和酸性（1.0 pH 3.0）的环境中，比如在黄石国家公园发现的环境。虽然SSV和STIV是最具特征的绿古菌病毒，但我们对这些独特的超嗜热病毒的了解有限。例如，对SSV和STIV基因组的序列分析未能确定大多数假定基因的同源物。因此，大多数病毒蛋白尚未被赋予任何功能，这些蛋白在病毒生命周期中扮演的角色仍然是一个谜。本项目利用结构生物学和生物化学(i)研究SSV和STIV蛋白质组的功能作用。这些蛋白质的结构将用x射线晶体学测定。在许多情况下，结构与蛋白质数据库中的结构的相似性有望提示病毒蛋白质的功能。此外，本项目寻求（ii）鉴定与特定病毒蛋白相互作用形成高阶复合物的病毒或宿主蛋白或DNA序列。鉴定这些相互作用的大分子将提供进一步的功能见解。总之，这些努力将有助于在分子水平上增加对SSV和STIV生命周期的了解，因此该项目代表了了解居住在这些极端环境中的独特病毒的重要一步。此外，这些病毒非常有趣，因为它们是理解高温下生命所需的生物化学和分子生物学的模型系统。通过它们与宿主机制的相互作用，它们为研究重要的生化事件提供了切入点，从而打开了一扇窗户，让我们了解仍知之甚少的绿原藻最基本的过程。从历史上看，病毒也是生物技术新酶的来源，特别是涉及核酸生物合成和修饰的酶。因此，从Crenarchaeal病毒中鉴定耐热酶可能在生物技术中具有重要的应用。最后，从所有三个生命领域的病毒的比较研究中获得的见解将有助于更好地理解病毒的发生和进化。更广泛的影响：蒙大拿州立大学热生物学研究所（TBI）正在进行的大部分工作都是通过TBI外展项目向公众传播的。关于嗜热病毒的工作是创伤性脑损伤的重点之一，因此是这些外联工作的主要重点。外展的合作伙伴包括国家公园管理局/黄石国家公园，并包括准备和审查公园内公开展示的材料。公园系统和公众一样，越来越意识到栖息在这些世界著名的热特征中的独特微生物，并正在努力增加公园内描述这些微生物的教育标志。该研究与PI、系里、大学和国家科学基金会的教育目标紧密结合。高中、本科、博士和博士后阶段的学生将接受生物化学、结构生物学和热生物学方面的重要培训。鼓励代表性不足的群体，特别是妇女和印第安人的参与，他们的参与有充分的记录。