C termini of aligned sequences of Ubls. (A) The alignment of parasite and human SUMO (hSUMO) homologs reveals that all species have one or more amino acids after the diglycine motif required for conjugation, thus indicating that processing is required before conjugation. P. falciparum, Plasmodium falciparum; T. gondii, Toxoplasma gondii; Th. annulata, Theileria annulata; Th. parva, Theileria parva; T. cruzi, Trypanosoma cruzi; T. brucei, Trypanosoma brucei; L. major, Leishmania major; E. histolytica, Entamoeba histolytica. (B) The alignment of parasite and yeast Atg8 homologs reveals that yeast and members of the kinetoplastid family, represented here by Trypanosoma brucei and Leishmania major, have residues beyond the conserved glycine but that members of the apicomplexan family, represented here by Plasmodium falciparum and Plasmodium berghei, have no additional residues, questioning the necessity of C-terminal processing before conjugation. Sc Atg8p, Saccharomyces cerevisiae Atg8p.

Maturation, conjugation, and deconjugation of ubiquitin and Ubls. Before conjugation, ubiquitin (Ub) and Ubls are processed from a precursor form to expose their C termini. The C-terminal extension varies in both length and sequence. They are then conjugated to substrates by a series of conjugation enzymes. Modified substrates are then subjected to or stimulate a variety of biological processes, depending on the modification type. Eventually the modifier is removed and recycled by ubiquitin- or Ubl-specific proteases that cleave the isopeptide bond generated during conjugation.