STRUCTURAL CHARACTERIZATION OF METAL TRANSPORTING PEPTIDES FROM MAMMALS & MICROO

哺乳动物金属转运肽的结构表征

• 批准号: 7370487
• 负责人: FARIDEH JALILEHVAND
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7370487
• 关键词: STRUCTURAL; CHARACTERIZATION; METAL; TRANSPORTING; PEPTIDES

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. Iron uptake in gram negative bacteria is accomplished through the use of siderophores (small modified peptides). Siderophores scavenge iron from the external environment and are then transported back into the bacterial cell. Siderophores complexed to toxic metals have been shown to be an effective antibacterial strategy. We will use the collected XAFS data to relate metal-binding properties, and structural changes. We will also use the high resolution XAFS data of the metal-binding sites to further refine our X-ray crystal structure data, which will be solved in parallel with these experiments. Iron uptake in humans is being investigated by the small peptide, gastrin17, which functions in the gastric lumen at acidic pH. Gastrin17 has been shown to bind two Fe-atoms, and although no structural data has yet been collected, evidence suggests these irons are bound as a dinuclear iron species. XAFS data will not only provide the first structural picture of the iron-binding site, but may also provide evidence of how closely the metals are bound with respect to one another. It has recently been postulated that the prion protein, involved in a range of deleterious neurological diseases, may function as a copper-sensing or copper-transporting protein at the synapse in mammals. Copper-binding has been linked to the formation of the disease state of the protein, although atomic resolution structural data is sparse. X-ray crystallography is of little use as the copper-binding region is highly unstructured in solution, as well as the solid state. Also, due to the paramagnetic nature of copper (Cu2+) NMR techniques are unable to probe the region immediately around the metal centre. We are therefore screening other metal ions with favourable NMR properties, using the XAFS technique to compare with the Cu2+-binding environment.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。革兰氏阴性细菌中的铁吸收是通过使用铁载体（小修饰肽）来实现的。铁载体从外部环境中清除铁，然后被运回细菌细胞中。与有毒金属络合的铁载体已被证明是一种有效的抗菌策略。我们将使用收集到的 XAFS 数据来关联金属结合特性和结构变化。我们还将使用金属结合位点的高分辨率 XAFS 数据来进一步细化我们的 X 射线晶体结构数据，这些数据将与这些实验并行解决。人类对铁的吸收正在通过小肽胃泌素 17 进行研究，胃泌素 17 在酸性 pH 条件下在胃腔中发挥作用。胃泌素 17 已被证明可以结合两个铁原子，尽管尚未收集到结构数据，但有证据表明这些铁以双核铁物种的形式结合。 XAFS 数据不仅可以提供铁结合位点的第一张结构图，还可以提供金属彼此结合程度的证据。最近有人推测，与一系列有害神经系统疾病有关的朊病毒蛋白可能在哺乳动物的突触中充当铜感应或铜转运蛋白。尽管原子分辨率结构数据很少，但铜结合与蛋白质疾病状态的形成有关。 X 射线晶体学几乎没有什么用处，因为铜结合区域在溶液和固态中都是高度非结构化的。 此外，由于铜 (Cu2+) 的顺磁性，核磁共振技术无法探测紧邻金属中心周围的区域。因此，我们正在筛选具有良好 NMR 特性的其他金属离子，使用 XAFS 技术与 Cu2+ 结合环境进行比较。