Abstract
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.
Highlights
Retroviral aspartic proteases, referred to as retropepsins, belong to family A2 of aspartic proteases
Coordinate files of most retroviral PRs and Ddi eukaryotic homologs were downloaded from the Protein Data Bank (PDB) database, with the exception of epsilonretrovirus PRs (Table 1), whose structures has not been determined experimentally to date
A coordinate file for a homodimeric Walleye epidermal hyperplasia virus type 1 (WEHV-1) PR was obtained by automated homology modeling (Figure 2B), using the SWISS-MODEL web server, and the proposed structure was used for multiple structure alignment
Summary
Retroviral aspartic proteases, referred to as retropepsins, belong to family A2 of aspartic proteases. The viral protease plays a significant role in the replication cycles of retroviruses by processing the viral Gag and Gag-Pol polyproteins. This limited proteolysis is an essential event of the viral life cycle; the viral proteases have become important targets of antiviral therapies. In addition to the active site motif, other structurally important regions, which are involved in dimer formation, are shared by the PRs as follows: (i) flap region, Int. J.
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