FIGURE 3.

Structure of FYCO1 LIR peptide bound to LC3B. A, electron density map of FYCO1 peptide on LC3. The F_o − F_c omit map of the FYCO1 peptide is contoured at 0.6 σ. B, overview of the LIR peptide (residues 1276–1288)(green) bound to LC3B (1–125)(magenta). Note that the structure in B is rotated 180 degrees relative to A. C, the side chains of the aromatic Phe¹²⁸⁰ residue and the hydrophobic Ile¹²⁸³ residues dock into hydrophobic pockets HP1 and HP2 of the LIR docking site of LC3B. D, detail of the electrostatic interaction between Arg¹⁰ in the N-terminal arm of LC3B and Asp¹²⁷⁷ located N-terminal to the core LIR. E, both Glu¹²⁸⁷ and Asp¹²⁸¹ of the LIR engage in electrostatic interactions with Arg⁷⁰ of LC3B. F, this interaction involving Arg⁷⁰ is not seen in the p62 LIR-LC3B complex as visualized in the structural comparison. G, the electrostatic interaction between FYCO1 Asp¹²⁸⁵ and His⁵⁷ in LC3B is likely a specificity determinant important for the preferential binding of FYCO1 to LC3A and -B. H, the most C-terminal Leu¹²⁸⁸ residue in the crystalized LIR peptide engages in hydrophobic interactions with Pro⁵⁵, Val⁵⁸, and Ile⁶⁶ of LC3B. I, sequence alignment of human ATG8 proteins generated with Clustal Omega (46). EPS image was generated with BOXSHADE. Shading indicates similarity. Solid circles indicate residues in LC3B required for interaction with FYCO1 LIR. Red solid circle indicates residue in LC3A/B conferring preference toward FYCO1 interaction.