ATG3 proteins possess a unique amphipathic α-helix essential for the Atg8/LC3 lipidation reaction

ABSTRACT

In our recent paper, we uncovered that ATG3 exhibits a large degree of structural dynamics on autophagic membranes to efficiently carry out LC3 lipidation. ATG3 proteins possess an amphipathic α-helix (AH) identified by a small number of bulky and hydrophobic residues. This biophysical fingerprint allows for transient membrane association of ATG3 and facilitates its enzymatic reaction. This study will pave the way for a structural and mechanistic understanding of how membrane association of ATG proteins is orchestrated during autophagosome formation.

KEYWORDS:

• All-atom MD simulation
• amphipathic α-helix
• ATG3
• LC3 lipidation
• membrane protein dynamics

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by PRESTO (JPMJPR20EC to T.N.) from Japan Science and Technology (JST), a grant-in-aid for Transformative Research Areas (B) (grant 21H05146 to T.N.) from the Japan Society for the Promotion of Science (JSPS), and a grant from the Japan Foundation for Applied Enzymology (to T.N.). S.A.T. was supported by The Francis Crick Institute, which receives its core funding from Cancer Research UK (CC2134 and CC2064), and the U.K. Medical Research Council (CC2134 and CC2064). This research was funded in whole, or in part, by the Wellcome Trust (CC2134 and CC2064). G.L. and R.C. acknowledge the support of the Frankfurt Institute of Advanced Studies, the LOEWE Center for Multiscale Modeling in Life Sciences of the state of Hesse, the CRC 1507: Membrane-associated Protein Assemblies, Machineries, and Supercomplexes, and computational resources and support by the Center for Scientific Computing of the Goethe University and the Julich Supercomputing Centre. G.L. acknowledges the graduate school iQbio. R.C. acknowledges the support of the International Max Planck Research School on Cellular Biophysics.