Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia.
Int J Mol Sci. 2022 Feb 6;23(3):1852. doi: 10.3390/ijms23031852.
Human dipeptidyl peptidase I (DPPI) belongs to the family of papain-like cysteine peptidases. Its distinctive features are the unique exclusion domain which enables the eponymous activity and homotetramerization of DPPI, and its dependence on chloride ions for enzymatic activity. The oligomeric state of DPPI is unique in this family of predominantly monomeric peptidases. However, a distant DPPI ortholog from has been shown to be monomeric, indicating that the oligomeric state of DPPI varies between lineages. The aim of this work was to study the evolution of DPPI, with particular attention to the structural features that determine its characteristic enzymatic activity and preferences, and to reconstruct the evolution of its oligomerization. We analyzed fifty-seven selected sequences of DPPI and confirmed its presence in three lineages, namely, Amorphea (including animals and Amoebozoa), Alveolates and the metamonad . The amino acid residues that bind the chloride ion are highly conserved in all species, indicating that the dependence on chloride ions for activity is an evolutionarily conserved feature of DPPI. The number of N-glycosylation sites is significantly increased in animals, particularly vertebrates. Analysis of homology models and subunit contacts suggests that oligomerization is likely restricted to DPPIs in the Amorphea group.
人二肽基肽酶 I（DPPI）属于木瓜蛋白酶样半胱氨酸肽酶家族。其独特特征是独特的排除域，使 DPPI 具有独特的活性和同源四聚化，以及对氯离子依赖性的酶活性。DPPI 的寡聚状态在主要为单体的肽酶家族中是独特的。然而，来自 的远缘 DPPI 同源物已被证明是单体，表明 DPPI 的寡聚状态在不同谱系之间存在差异。本工作旨在研究 DPPI 的进化，特别关注决定其特征酶活性和偏好的结构特征，并重建其寡聚化的进化。我们分析了 57 个选定的 DPPI 序列，并证实其存在于三个谱系中，即无定形生物（包括动物和变形虫）、肺泡和原生动物 。结合氯离子的氨基酸残基在所有物种中高度保守，表明对氯离子依赖性的活性是 DPPI 的一个进化保守特征。N-糖基化位点的数量在动物中显著增加，特别是在脊椎动物中。同源模型和亚基接触的分析表明，寡聚化可能仅限于无定形生物组中的 DPPI。
