Structural and functional elucidation of the peroxisomal AAA+ complex

过氧化物酶体 AAA 复合物的结构和功能阐明

• 批准号: 383680709
• 负责人: Professorin Dr. Petra Wendler
• 金额: --
• 依托单位: Institut für Biochemie und Biologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/383680709?language=en
• 关键词: Structural; functional; elucidation; peroxisomal; AAA+

Peroxisomes are membrane-encapsulated cell organelles which are responsible for life-threatening oxidative metabolic processes such as the breakdown of peroxides or fatty acids and the formation of ether phospholipids. In yeast, at least 32 so-called Pex proteins are responsible for the biogenesis and maintenance of peroxisomes. Pex1 and Pex6 are ATPases of the AAA + (ATPases associated with various cellular activities) superfamily that drive the transport of folded proteins across the peroxisomal membrane. Both proteins are essential for peroxisomal biogenesis. Mutations in human Pex1 and Pex6 are the most common cause of severe autosomal recessive diseases of the Zellweger syndrome spectrum. The aim of the project is the structural and functional characterization of the human Pex1 / 6 complex using cryo-electron microscopy and single particle analysis. For this purpose, snapshots of the conformational changes during a working cycle of the complex will be structurally represented and the interaction between Pex1 and Pex6 will be investigated. Furthermore, the effects of a prominent mutation in Pex1 will be examined biochemically and structurally.

过氧化物酶体是膜包封的细胞器，其负责威胁生命的氧化代谢过程，例如过氧化物或脂肪酸的分解和醚磷脂的形成。在酵母中，至少有32种所谓的Pex蛋白负责过氧化物酶体的生物发生和维持。Pex 1和Pex 6是AAA +（与各种细胞活性相关的ATP酶）超家族的ATP酶，其驱动折叠蛋白质穿过过氧化物酶体膜的运输。这两种蛋白质都是过氧化物酶体生物合成所必需的。人类Pex 1和Pex 6突变是Zellweger综合征谱系中严重常染色体隐性遗传疾病的最常见原因。该项目的目的是使用冷冻电子显微镜和单颗粒分析对人类Pex 1/ 6复合物进行结构和功能表征。为此，快照的构象变化在复杂的工作周期将结构表示和Pex 1和Pex 6之间的相互作用将进行调查。此外，在Pex 1的突出突变的影响将进行生化和结构检查。