TIME-RESOLVED SOLUTION X-RAY SCATTERING STUDIES ON THE HEPATITIS B CAPSID PROTEI

乙型肝炎衣壳蛋白的时间分辨溶液X射线散射研究

• 批准号: 8169937
• 负责人: HIROTSUGU TSURUTA
• 金额: $ 0.24万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169937
• 关键词: Antiviral Agents; Capsid; Capsid Proteins; Complex; Computer Retrieval of Information on Scientific Projects Database; Computer Simulation; Drug Compounding; Escherichia coli; Exhibits; Funding; Future; Goals; Grant; Hepatitis; Hepatitis B Virus; Human; Institution; Kinetics; Malignant Neoplasms; Measurement; Nucleosome Core Particle; Pathway interactions; Pharmaceutical Preparations; Process; Proteins; Proteus; Reaction; Research; Research Personnel; Resources; Shunt Device; Sodium Chloride; Solutions; Source; Therapeutic; Time; Time Study; United States National Institutes of Health; Urea; Vaccines; Viral; Virus; Virus-like particle; combat; interest; pathogen; virus core

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. SAXS will be applied to understand the assembly and disassembly of Hepatitis B virus (HBV) cores (non-infectious virus-like particles produced from E. coli expressed protein) and to investigate the mechanism of anti-viral drug-induced core particle disruption. HBV is a major pathogen and one of the most prevalent causative agents of cancer in humans. While effective vaccines are available, it remains of significant interest to add to the battery of antiviral therapeutics that can combat the virus. The goal of the studies is to understand mechanistically how a complex viral assembly is constructed and how capsid-targeted drug compounds can shunt the assembly reactions off-pathway. We recently studied the capsid disassembly process which exhibited a distinct kinetic profile predicted by computational models. We also conducted static x-ray scattering measurements of the capsid protein as a function of urea concentration prior to planned time-resolved measurements. We have been able to determine that the capsid protein can be kept unassembled in the dimeric form in the presence of 50 mM for a few days or longer. In the next step, we plan on conducing time-resolved studies of assembly induced a salt concentration jump via a rapid stopped-flow mixing. We anticipate to observe initial steps of the capsid assembly as a function of time and study the effects of potential drug compounds modifying assembly kinetics in near future.

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