The role of FIP200 in Phagophore formation during Autophagy

Abstract

The Moeller Molecular Modeling Team in conjunction with Dr. Jiajie Diao at the University of Cincinnati Medical College used 3D modeling and printing technology to study the vital role of the focal adhesion kinase family interacting protein of 200 kD (FIP200) in the autophagy process. The cellular process of autophagy is enabled by formation of autophagosomes, a double membraned structure that isolates substrates designated by the cell to be eliminated by autophagy. FIP200 is a 200 kD subunit of the ULK1 complex which facilitates the formation of phagophores, the first step in autophagosome formation. An ULK1 protein kinase is necessary for the activation of the ULK1 complex during autophagosome formation. The positively charged “claw domain” area at the C‐terminal region of FIP200 interacts with p62, a receptor protein, which delivers ubiquitinated cargo proteins bound to LC3B, a central regulator for autophagosome formation. After the binding of these proteins, the autophagosome forms around the ubiquitinated cargo and continues to the next step of the autophagy process.