Structure and molecular function of the WD-40 repeat containing autophagy proteins Atg18, Atg21 and Hsv2 (B04)

• Subject Area: Structural Biology
• Term: from 2010 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 105286809

Atg18, Atg21 and Hsv2 belong to the PROPPIN family (-propellers that bind PIPs), which differently affect autophagic subtypes. -propeller proteins are platforms for multi-protein complexes. We want to dissect the composition, structure and molecular function of Atg18, Atg21 and Hsv2 complexes and understand their dynamic assembly and disassembly. In the crystal structure of KlHsv2 we uncovered two PI3P-binding sites. Now, we show that Atg21 binds via PI3P to growing autophagosomes, where it arranges PI3P-dependent the Atg8 lipidation machinery in its functional orientation.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 860: Integrative Structural Biology of Dynamic Macromolecular Assemblies
• Applicant Institution: Georg-August-Universität Göttingen
• Project Heads: Professor Dr. Ralf Ficner, from 10/2016 until 6/2018; Dr. Karin Kühnel, until 9/2016; Professor Dr. Michael Thumm