Structural and functional elucidation of the peroxisomal AAA+ complex

• Applicant: Professorin Dr. Petra Wendler
• Subject Area: Structural Biology ; Cell Biology
• Term: from 2017 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 383680709

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.

• DFG Programme: Research Grants