GABARAP interacts with EGFR — supporting the unique role of this hAtg8 protein during receptor trafficking

The human Atg8 family member GABARAP is involved in numerous autophagy‐related and ‐unrelated processes. We recently observed that specifically the deficiency of GABARAP enhances epidermal growth factor receptor (EGFR) degradation upon ligand stimulation. Here, we report on two putative LC3‐interacting regions (LIRs) within EGFR, the first of which (LIR1) is selected as a GABARAP binding site in silico. Indeed, in vitro interaction studies reveal preferential binding of LIR1 to GABARAP and GABARAPL1. Our X‐ray data demonstrate interaction of core LIR1 residues FLPV with both hydrophobic pockets of GABARAP suggesting canonical binding. Although LIR1 occupies the LIR docking site, GABARAP Y49 and L50 appear dispensable in this case. Our data support the hypothesis that GABARAP affects the fate of EGFR at least in part through direct binding. GABARAP is a human Atg8 family member, and its deficiency enhances epidermal growth factor receptor (EGFR) degradation upon stimulation. We report on two putative LC3‐interacting regions (LIRs) on EGFR, the first of which (LIR1) appears to preferentially interact with GABARAP both in vitro and in silico. Within the LIR1–GABARAP complex structure, both hydrophobic pockets of GABARAP interact with LIR1 residues FLPV, suggesting canonical binding. GABARAP, therefore, might influence the fate of EGFR by direct binding.