VIRUSES: FROM PARTICLES TO PROTEOMICS

病毒：从粒子到蛋白质组学

• 批准号: 7721028
• 负责人: BRIAN P BOTHNER
• 金额: $ 12.85万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721028
• 关键词: Antiviral Agents; Apoptotic; Atomic Force Microscopy; Biology; Canine Parvovirus; Capsid; Caspase; Cells; Cessation of life; Complex; Computer Retrieval of Information on Scientific Projects Database; Cysteine Protease; Dependovirus; Equilibrium; Frequencies; Funding; Grant; Hepatitis B Virus; Infection; Institution; Investigation; Knowledge; Lead; Measurement; Molecular Conformation; Motion; Mus; Norovirus; Parvovirus; Phase; Process; Property; Protein Dynamics; Proteins; Proteomics; Publications; Quartz; Range; Rate; Research; Research Personnel; Resolution; Resources; Solutions; Source; System; United States National Institutes of Health; Virion; Virus; Virus Diseases; Work; base; cowpea chlorotic mottle virus; novel; pathogen; protein function; three dimensional structure

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. The solution-phase protein motion that is part of a multi-component complex is rarely obvious from the high resolution three-dimensional structure. Protein function is intimately connected to dynamics and therefore knowledge of the frequency, range, and coordination of motion by supramolecular complexes is critical to understanding how they function. In this project, viruses are a paradigm for studying protein dynamics in supramolecular complexes. In the past year, significant steps have been made in Dr. Bothner's studies on the biophysical properties of virus particles. Systems currently under investigation include Hepatitis B virus, Adeno-associated virus, Canine Parvovirus, Cowpea Chlorotic Mottle Virus. A recent publication on Hepatitis B virus presents the first measurements of the rates and equilibria for protein motion in a megadalton complex. Breakthroughs have also been made in understanding how pH values, relevant to cell entry, modulates the stability and dynamics of parvoviruses. Through the use of a quartz crystal microbalance and atomic force microscopy the viscoelastic properties of a virus capsid in different conformation has been completed. Viruses are obligate cellular pathogens and therefore many cellular proteins are critical for viral infection, replication, and release from a host cell. Using proteomics-based approaches, Dr. Bothner's lab is seeking to identify cellular proteins that are hijacked by viruses during the infection process. The significance of this work is two fold; the basic biology of viruses can be elucidated and novel targets for antiviral agents will be identified. Dr. Bothner's work on murine norovirus infection of mouse RAW cells has lead to the identification of cysteine proteases, upstream of the mitochorndria that are involved with infection. Surprisingly, inhibition of caspases in general during infection, leads to rapid, non-apoptotic death.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 作为多组分复合体的一部分，溶液相蛋白质的运动从高分辨率的三维结构中很少明显。蛋白质的功能与动力学密切相关，因此了解超分子复合体运动的频率、范围和协调性对于理解它们的功能至关重要。在这个项目中，病毒是研究超分子复合体中蛋白质动力学的一个范例。在过去的一年里，博特纳博士对病毒颗粒的生物物理特性的研究取得了重大进展。目前正在调查的病毒系统包括乙肝病毒、腺相关病毒、犬细小病毒、豌豆褪绿斑驳病毒。最近发表的一篇关于乙肝病毒的文章首次测量了蛋白质在百万吨复合体中的运动速度和平衡。在理解与细胞进入相关的pH值如何调节细小病毒的稳定性和动态方面也取得了突破。通过使用石英晶体微天平和原子力显微镜，完成了不同构象的病毒衣壳的粘弹性性质。 病毒是专有的细胞病原体，因此许多细胞蛋白对病毒感染、复制和从宿主细胞释放至关重要。博特纳博士的实验室使用基于蛋白质组学的方法，试图识别在感染过程中被病毒劫持的细胞蛋白质。这项工作的意义是双重的；病毒的基本生物学可以被阐明，抗病毒药物的新靶点将被确定。博特纳博士对小鼠原始细胞感染小鼠诺沃克病毒的研究导致了半胱氨酸蛋白酶的鉴定，半胱氨酸蛋白酶位于线粒体上游，与感染有关。令人惊讶的是，在感染期间抑制半胱氨酸酶一般会导致快速、非凋亡性死亡。