ASSEMBLY, DYNAMICS, AND INFECTIVITY OF VIRUSES USING A MASS SPECTROMETRY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 作为多组分复合物的一部分的溶液相蛋白质运动很少从高分辨率三维结构中明显看出。 蛋白质功能与动力学密切相关，因此了解超分子复合物运动的频率、范围和协调对于理解它们如何发挥作用至关重要。 Bothner博士的实验室使用病毒作为研究超分子复合物中蛋白质动力学的范例。 他们最近首次测量了兆道尔顿复合物中大规模蛋白质运动的自由能和平衡性质。 目前正在研究的系统包括B型肝炎、诺瓦克病毒和犬细小病毒。 Bothner博士的工作证明了蛋白质动力学是病毒颗粒的固有特征。 在每种情况下，所鉴定的蛋白质结构域与在感染中起重要作用的结构域相关。病毒是专性细胞病原体，因此许多细胞蛋白对于病毒感染、复制和从宿主细胞释放至关重要。 使用基于蛋白质组学的方法，我们正在寻求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，可以阐明病毒的基本生物学，并确定抗病毒剂的新靶点。

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. Dr. Bothner's lab uses viruses as a paradigm for studying protein dynamics in supramolecular complexes. They have recently made the first measurements of the free energy and equilibrium properties for large scale protein motion within a megadalton complex. Systems currently under investigation include Hepatitis B, Norwalk, and Canine Parvovirus. Dr. Bothner's work has demonstrated that protein dynamics are an inherent feature of virus particles. In each case, the identified protein domains correlate with domains that play important roles in infection. 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, we are 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.