FOLDING AND ASSEMBLY OF DIMERIC BETA-BARREL PROTEINS

二聚体 β-桶蛋白的折叠和组装

• 批准号: 7369137
• 负责人: Osman Bilsel
• 金额: $ 2.97万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7369137
• 关键词: FOLDING; ASSEMBLY; DIMERIC; BETA; BARREL

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. An understanding of how a random-coil polypeptide chain folds into a functional enzyme with a unique three-dimensional structure is one of the most significant unresolved questions in biology. Success in solving this fundamental problem will lead to significant advances in biotechnology and treatment of diseases related to protein misfolding. Amyotrophic lateral sclerosis (Lou Gehrig's disease) is an example of a neurodegenerative disease in which misfolding of a protein (Cu, Zn superoxide dismutase, SOD) has been hypothesized to play a role in the gain-of-function toxicity. Understanding the energy landscape of this dimeric beta-barrel protein is therefore important for revealing the dynamics and structural properties of partially-folded states that may be relevant to toxicity. To test the folding mechanism and probe the structural properties of the partially folded states of SOD we conducted a time-resolved SAXS study of apo-SOD. The goal of the study was to determine the sequence in which collapse, secondary structure formation and dimerization occur. This study was part of a comprehensive NIH-funded project examining the folding mechanism of two dimeric beta-barrel proteins, apo-SOD and HIV-1 protease.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。了解无规卷曲多肽链如何折叠成具有独特三维结构的功能酶是生物学中最重要的未解决问题之一。成功解决这一基本问题将导致生物技术和蛋白质错误折叠相关疾病治疗的重大进展。 肌萎缩性侧索硬化症（Lou Gehrig病）是神经退行性疾病的一个例子，其中蛋白质（Cu，Zn超氧化物歧化酶，SOD）的错误折叠已被假设在功能获得性毒性中发挥作用。因此，了解这种二聚体β桶蛋白的能量景观对于揭示可能与毒性相关的部分折叠状态的动力学和结构特性非常重要。为了测试SOD的折叠机制和探测部分折叠状态的结构特性，我们对apo-SOD进行了时间分辨SAXS研究。该研究的目的是确定塌陷、二级结构形成和二聚化发生的顺序。这项研究是NIH资助的一个综合项目的一部分，该项目研究了两种二聚体β-桶蛋白（apo-SOD和HIV-1蛋白酶）的折叠机制。