SAXS OF THE COMPLEX OF ANTHRAX TOXINS AND HUMAN INSULIN DEGRADING ENZYME

炭疽毒素与人胰岛素降解酶复合物的SAXS

• 批准号: 8168652
• 负责人: WEI-JEN TANG
• 金额: $ 0.36万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168652
• 关键词: Address; Adenylate Cyclase; Amyloid beta-Protein; Anthrax disease; Bacillus anthracis; Bacteria; Bacterial Toxins; Binding; Binding Sites; Biological Process; Bordetella pertussis; Calmodulin; Cell Surface Receptors; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; Diabetes Mellitus; Disease; Enzymes; Funding; Grant; Human; Institution; Insulin; Insulinase; Lipase; Metalloproteases; Mitochondria; Peptide Hydrolases; Pertussis; Play; Process; Proteins; Research; Research Personnel; Resources; Role; Set protein; Solutions; Source; Structure; Toxin; United States National Institutes of Health; anthrax edema factor; anthrax protective factor; anthrax toxin; edema factor; insight; protein protein interaction

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. Protein-protein interaction is a process that controls the diverse biological functions. We will use SAXS to address the complex protein-protein interactions in solution by studying human proteases and bacterial toxins. First, we will study two human metalloproteases, insulin degrading enzyme (IDE) and presequence peptidase (PreP). IDE plays a key role in the clearance of insulin and amyloid beta, peptides vital for the progression of diabetes and Alzheimer¿s disease, respectively. PreP degrades mitochondrial presequences and amyloid beta so that it plays a key role to maintain integrity of mitochondria. We propose to use SAXS on study the oligomerization, the conformational switch, and substrate binding of these enzymes. Second set of proteins are bacterial toxins secreted by Bacillus anthracis, and Bordetella pertussis, the etiologic agent for anthrax and whooping cough. Our lab has solved the crystal structures of anthrax edema factor (EF), anthrolysin O (ALO), and pertussis CyaA. EF is an adenylyl cyclase toxin that binds anthrax protective antigen for its cell entrance and binds calmodulin for its catalytic activation. Pertussis CyaA also requires the binding of calmodulin for its catalytic activation. However CyaA has the calmodulin-binding site distinct from that of EF. For ALO, it needs to oligomerize for its pore-forming activity as well as binds to cell surface receptor. In addition, anthrax bacteria secrete approximately 400 proteins and of those, we have chosen several lipases and proteases to study their functions. SAXS will be used to gain the new insights for the interaction of these toxins with their partner proteins.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 蛋白质蛋白质相互作用是控制潜水生物学功能的过程。我们将通过研究人蛋白和细菌毒素来使用SAX来解决溶液中复杂的蛋白质蛋白相互作用。首先，我们将研究两个人类金属蛋白酶，胰岛素降解酶（IDE）和presequence肽（PREP）。 IDE在清除胰岛素和淀粉样蛋白β的清除率中起着关键作用，对糖尿病和阿尔茨海默氏病的进展至关重要。预备会降解线粒体的presequence和淀粉样蛋白β，因此它在维持线粒体的完整性方面起着关键作用。我们建议将SAXS用于研究这些酶的寡聚化，概念开关和底物结合。第二组蛋白是炭疽芽孢杆菌分泌的细菌毒素，以及百日咳Bordetella ofterella蛋白，这是炭疽病和百日咳的病因学剂。我们的实验室解决了炭疽水肿因子（EF），Anthroysin O（ALO）和百日咳CYAA的晶体结构。 EF是一种腺苷酸环化酶毒素，结合了炭疽抗原的细胞入口，并结合钙调蛋白以催化活化。百日咳CYAA还需要钙调蛋白的催化活化。但是，CYAA具有与EF不同的钙调蛋白结合位点。对于ALO而言，它需要使其形成孔的活性以及与细胞表面受体结合而进行寡聚。此外，炭疽细菌分泌了大约400种蛋白质，其中我们选择了几种脂肪酶和蛋白来研究其功能。 SAX将用于获得这些毒素与伴侣蛋白的相互作用的新见解。