Mechanistic studies of Legionella effector RavZ function in host autophagy using semi-synthetic LC3 proteins

• Applicant: Dr. Yaowen Wu
• Subject Area: Biochemistry
• Term: from 2012 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 223373492

Eukaryotic cells defend against invading pathogens by autophagy pathway, a process termed as xenophagy. Legionella pneumophila is an intracellular pathogen that manipulates evolutionarily conserved autophagy by injecting a bacterial virulence effector protein RavZ, which detaches LC3 proteins coupled to phosphatidylethanolamine (PE) on autophagosome membranes. The molecular mechanism of such a process remains elusive. The studies on RavZ function are impeded because of the lack of the recombinant LC3-PE and the appraoches to manipulate LC3-PE structure. Herein, I propose to elucidate the mechanistic basis of RavZ function using a combination of chemical, biophysical and structure biological tools. The semi-synthetic LC3 proteins will render such studies possible, and provide valuable tools to understand how pathogenic effectors manipulate endogenous autophagy machinery.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1623: Chemoselective Reactions for the Synthesis and Application of Functional Proteins