Dimer Interface Organization is a Main Determinant of Intermonomeric Interactions and Correlates with Evolutionary Relationships of Retroviral and Retroviral-Like Ddi1 and Ddi2 Proteases.

The life cycles of retroviruses rely on the limited proteolysis catalyzed by the viral protease. Numerous eukaryotic organisms also express endogenously such proteases, which originate from retrotransposons or retroviruses, including DNA damage-inducible 1 and 2 (Ddi1 and Ddi2, respectively) proteins. In this study, we performed a comparative analysis based on the structural data currently available in Protein Data Bank (PDB) and Structural summaries of PDB entries (PDBsum) databases, with a special emphasis on the regions involved in dimerization of retroviral and retroviral-like Ddi proteases. In addition to Ddi1 and Ddi2, at least one member of all seven genera of the Retroviridae family was included in this comparison. We found that the studied retroviral and non-viral proteases show differences in the mode of dimerization and density of intermonomeric contacts, and distribution of the structural characteristics is in agreement with their evolutionary relationships. Multiple sequence and structure alignments revealed that the interactions between the subunits depend mainly on the overall organization of the dimer interface. We think that better understanding of the general and specific features of proteases may support the characterization of retroviral-like proteases.