Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, 4032 Debrecen, Hungary.
Int J Mol Sci. 2020 Feb 17;21(4):1352. doi: 10.3390/ijms21041352.
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 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.
逆转录病毒的生命周期依赖于病毒蛋白酶的有限蛋白水解催化。许多真核生物也表达内源性的此类蛋白酶，这些蛋白酶来源于逆转座子或逆转录病毒，包括 DNA 损伤诱导蛋白 1 和 2（分别为 Ddi1 和 Ddi2）。在这项研究中，我们根据目前可从蛋白数据库（PDB）和 PDB 条目结构摘要（PDBsum）数据库中获得的结构数据进行了比较分析，特别强调了涉及逆转录病毒和逆转录病毒样 Ddi 蛋白酶二聚化的区域。除了 Ddi1 和 Ddi2 之外，该比较还包括家族的七个属中的至少一个成员。我们发现，所研究的逆转录病毒和非病毒蛋白酶在二聚化模式和分子间接触密度方面存在差异，结构特征的分布与它们的进化关系一致。多重序列和结构比对表明，亚基之间的相互作用主要取决于二聚体界面的整体组织。我们认为，更好地理解蛋白酶的一般和特定特征可能有助于对逆转录病毒样蛋白酶进行特征描述。
