Linear motifs regulating protein secretion, sorting and autophagy in Leishmania parasites are diverged with respect to their host equivalents
Fig 3
A: Our evolutionary model of ATG8 protein groups in Leishmaniinae. For each paralog, the surface mutations expected to block LIR binding are shown in red, while the novel invariant surface is in orange. The small structural figures show matching protein surfaces from the same angle. Predicted ATG4 cleavage sites (P-4 to P-1) for each protein group are exemplified by a sequence written in gray below each group name. B: The ATG8A, ATG8B and ATG8C genes are typically found in two tandem arrays within leishmanial genomes but their copy numbers vary highly across species. C: The preserved LIR peptide-binding ability of ATG8 proteins is illustrated by a simulated model between this protein and a Leishmania LIR motif model peptide, similar to the ones seen in conserved autophagy apparatus proteins ATG2, ATG3 and ATG4 (frequency logos from proteins in group Discoba written below). D: The simulated complexes between ATG8 and the enzyme ATG4.2 and between ATG8C and ATG4.2 are highly similar and betray a potential existence of a LIR-equivalent motif for atypical ATG8s.