CHEETAH Center for the Structural Biology of HIV Infection, Restriction, and Viral Dynamics

CHEETAH HIV 感染、限制和病毒动力学结构生物学中心

基本信息

批准号：
10663358
负责人：
CHRISTOPHER P. HILL
金额：
$ 22.33万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-11 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10663358
关键词：
Bacterial Proteins Binding Biochemistry Biological Assay Biology Biology of HIV Infection Biophysics Calorimetry Circular Dichroism Collaborations Complement Complex Computer software Cryoelectron Microscopy Crystallization Data Data Collection Development Experimental Designs Fluorescence Polarization Foundations Growth HIV HIV-1 Kinetics Laboratories Micro Electron Diffraction Negative Staining Process Production Proteins RNA Recombinants Recording of previous events Resolution Resources Robotics Roentgen Rays Role Sampling Scholars Program Services Structure Surface Plasmon Resonance Synchrotrons System Techniques Thermodynamics Titrations Training Universities Utah Validation Viral X-Ray Crystallography analytical ultracentrifugation biophysical properties computerized data processing design design and construction insight instrumentation macromolecule member novel therapeutic intervention particle programs protein expression protein folding protein purification screening small molecule structural biology success tool visiting scholar

项目摘要

CORE SUMMARY The ability to express, purify, characterize, and determine the structures of recombinant HIV-related proteins, RNAs, and their complexes is central to the success of all of our Scientific Projects and Cores. Our Protein Production, Biophysical Characterization, and Structure Determination Core (Core 3) is designed to ensure that all CHEETAH Center members and trainees have access to state-of-the-art instrumentation and expertise in construct design, eukaryotic and bacterial protein expression, biophysical characterization, X-ray crystallography, cryoEM, and training in biophysics and structural biology. Services offered by Core 3 will build on our history of successes in expressing, characterizing, and determining the structures of HIV-related proteins and complexes. Component 1 (Expression and Purification of Proteins and Complexes) will support CHEETAH Center laboratories in the production of proteins needed to gain mechanistic insight into processes important for HIV-1 biology, with potential to inform the development of novel therapeutic approaches. All associated resources are located in the Department of Biochemistry at the University of Utah. Component 2 (Biophysical Characterization) will define and validate the biophysical properties of proteins and complexes produced by CHEETAH Center members using state-of-the-art techniques and instrumentation. These data will provide mechanistic insights, and will support and complement high-resolution structural studies. The associated instrumentation is housed in the Department of Biochemistry at the University of Utah, and experimental design, implementation, and data processing are conducted in collaboration with CHEETAH Center members. This Component will also perform a key training role in our Visiting Scholars Program. Component 3 (Structure Determination) will support CHEETAH Center laboratories by determining structures of proteins and complexes that are important for HIV-1 biology. Structures will be determined by single particle cryoEM or X-ray crystallography, thereby providing a foundation for mechanistic understanding with potential to inform the development of novel therapeutic approaches. This Component will also perform a key training role in our Visiting Scholars Program.

核心摘要表达、纯化、表征和确定重组 HIV 相关蛋白、RNA 和结构的能力它们的复合体对于我们所有科学项目和核心的成功至关重要。我们的蛋白质生产，生物物理表征和结构确定核心（核心 3）旨在确保所有 CHEETAH 中心成员和学员可以使用最先进的仪器和构建设计、真核和细菌蛋白质方面的专业知识表达、生物物理表征、X 射线晶体学、冷冻电镜以及生物物理学和结构生物学培训。 Core 3 提供的服务将建立在我们在表达、表征和确定结构方面的成功历史之上 HIV相关蛋白质和复合物。第 1 部分（蛋白质和复合物的表达和纯化）将支持 CHEETAH 中心实验室生产所需的蛋白质，以获得对 HIV-1 生物学重要过程的机制洞察，有潜力为新的治疗方法的开发提供信息。所有相关资源均位于犹他大学生物化学系。第 2 部分（生物物理表征）将定义和验证蛋白质和复合物的生物物理特性由猎豹中心成员使用最先进的技术和仪器制作。这些数据将提供机制见解，并将支持和补充高分辨率结构研究。相关仪器是位于犹他大学生物化学系，实验设计、实施和数据处理是与 CHEETAH 中心成员合作进行的。该组件还将执行一个关键的操作我们的访问学者计划中的培训角色。第 3 部分（结构测定）将通过测定蛋白质结构来支持 CHEETAH 中心实验室以及对 HIV-1 生物学很重要的复合物。结构将通过单粒子冷冻电镜或 X 射线确定晶体学，从而为机械理解提供了基础，有可能为晶体学的发展提供信息新的治疗方法。该部分还将在我们的访问学者计划中发挥关键的培训作用。