Analysis of the formation of autophagosomes by semisynthetic LC3 proteins

The interest on autophagy, an evolutionarily conserved process in eukaryotes, has enormously increased in the last years, since the malfunctioning of autophagy is involved in many diseases such as cancer or neurodegenerative states. Autophagosome formation is the key process in autophagy. Despite extensive work, the model of autophagosome formation is not yet fully established. Some important questions remain to be elusive, such as where the bona fide marker protein of autophagosome, LC3, is lipidated, how lipidated LC3 functions in autophagosome formation, and how the proteins for LC3 lipidation and delipidation are involved in autophagosome formation.

Although genetic approaches have been powerful to dissect autophagosome formation process, intrinsic limitations include the lack of acute manipulation in protein activity. We will prepare semi-synthetic LC3 and lipidated LC3 proteins and use them to monitor dynamics of autophagosome formation in vitro and in cells. The semi-synthetic LC3 proteins will render such studies possible, and provide valuable tools for dissecting the autophagosome formation process. The project is multidisciplinary. On one hand, the establishment of semi-synthetic LC3 proteins will open up a new avenue for studying autophagosome formation. On the other hand, the application of the tool will shed light on the mechanism of autophagosome formation.

Dr. Yaowen Wu
Max-Planck-Institut für molekulare Physiologie

Tel.: +49 231 133 - 2364
Fax: +49 231 133 - 2399

Email Dr. Wu

Publications within the SPP 1623 project

A. Yang, I. Hacheney, Y.W. Wu
Bioorg & Med Chemistry 2017, 25(18), 4971-4976
Semisynthesis of qutophagy protein LC3 conjugates.
Link to the article

S. Pantoom, A. Yang, Y.W. Wu
Autophagy 2017, 13(8), 1467-1469
Lift and cut: Anti-host autophagy mechanism of Legionella pneumophila.
Link to the article

X. Chen, M. Venkatachalapathy, D. Kamps, S. Weigel, R. Kumar, M. Orlich, R. Garrecht, M. Hirtz, C.M. Niemeyer, Y.W. Wu, L. Dehmelt
Angew. Chem. Int. Ed. 2017, 56(21), 5916-5920
"Molecular Activity painting": Switch-like, Light-Controlled Perturbations inside Living Cells (Hot paper, inside cover story)
Link to the article

A.Yang, S. Pantoom, Y.W. Wu
Elife 2017, pii:e23905, DOI: 10.7554/eLife.23905
Elucidation of the anti-autophagy mechanism of the Legionella effector RavZ using semisynthetic LC3 proteins.
Link to the article

S. Voss, D.M. Krüger, O. Koch. Y.W. Wu
Proc. Natl. Acad. Sci USA 2016, 113(50), 14348-14343
Spatiotemporal imaging of small GTPases activity in live cells.
Link to the article

L. Zhao, C. Ehrt, O. Koch, Y.W. Wu
Angew. Chem. Int. Ed.2016, 55(28), 8129-8133.
One-Pot N2C/C2C/N2N Ligation To Trap Weak Protein-Protein Interactions.
Link to the article

X. Chen Y.W. Wu
Org. Biomol. Chem. 2016, 14(24), 5417-5439.
Selective chemical labeling of proteins.
Link to the article