Evolutionary analysis of dipeptidyl peptidase I

Varda, Nina (author), Novinec, Marko (author)

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 Plasmodium falciparum 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 Giardia. 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.

• Language: English
• Keywords: oligomerization, molecular evolution, cathepsin C
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: 12 str.
• Numbering: Vol. 23, iss. 3, art. 1852
• PID: 20.500.12556/RUL-137349
• UDC: 577.15
• ISSN on article: 1661-6596
• DOI: 10.3390/ijms23031852
• COBISS.SI-ID: 96531459
• Publication date in RUL: 13.06.2022

Record is a part of a journal

• Title: International journal of molecular sciences
• Shortened title: Int. j. mol. sci.
• Publisher: MDPI
• ISSN: 1661-6596
• COBISS.SI-ID: 36217605

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 06.02.2022

Secondary language

• Language: Slovenian
• Keywords: oligomerizacija, molekularna evolucija, katepsin C

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: N1-0211
• Name: Uvedba kooperativnosti v peptidaze za izboljšanje njihove aktivnosti in uravnavanja

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0140
• Name: Proteoliza in njena regulacija