Processing and maturation of cathepsin C zymogen: a biochemical and molecular modeling analysis

Anne-Sophie Lamort , Yveline Hamon , Cezary Czaplewski , Artur Giełdoń , Seda Seren , Laurent Coquet , Fabien Lecaille , Adam Lesner , Gilles Lalmanach , Francis Gauthier , Dieter Jenne , Brice Korkmaz


Cysteine cathepsin C (CatC) is a ubiquitously expressed, lysosomal aminopeptidase involved in the activation of zymogens of immune-cell-associated serine proteinases (elastase, cathepsin G, proteinase 3, neutrophil serine proteinase 4, lymphocyte granzymes, and mast cell chymases). CatC is first synthetized as an inactive zymogen containing an intramolecular chain propeptide, the dimeric form of which is processed into the mature tetrameric form by proteolytic cleavages. A molecular modeling analysis of proCatC indicated that its propeptide displayed a similar fold to those of other lysosomal cysteine cathepsins, and could be involved in dimer formation. Our in vitro experiments revealed that human proCatC was processed and activated by CatF, CatK, and CatV in two consecutive steps of maturation, as reported for CatL and CatS previously. The unique positioning of the propeptide domains in the proCatC dimer complex allows this order of cleavages to be understood. The missense mutation Leu172Pro within the propeptide region associated with the Papillon–Lefèvre and Haim–Munk syndrome altered the proform stability as well as the maturation of the recombinant Leu172Pro proform.
Author Anne-Sophie Lamort - [Inserm]
Anne-Sophie Lamort,,
, Yveline Hamon - [Inserm]
Yveline Hamon,,
, Cezary Czaplewski (FCh / DTCh / LSP)
Cezary Czaplewski,,
- Laboratory of Simulation of Polymers
, Artur Giełdoń (FCh / DTCh / LSP)
Artur Giełdoń,,
- Laboratory of Simulation of Polymers
, Seda Seren - [Inserm]
Seda Seren,,
, Laurent Coquet - [Normandie Université]
Laurent Coquet,,
, Fabien Lecaille - [Inserm]
Fabien Lecaille,,
, Adam Lesner (FCh / DET / LBAN)
Adam Lesner,,
- Laboratory of Biochemical Analytics and Nanodiagnostics
, Gilles Lalmanach - [Inserm]
Gilles Lalmanach,,
, Francis Gauthier - [Inserm]
Francis Gauthier,,
et al.`
Journal seriesInternational Journal of Molecular Sciences, ISSN 1422-0067, (N/A 140 pkt)
Issue year2019
Publication size in sheets0.7
Article number4747
Keywords in EnglishCathepsin C, cysteine cathepsin, zymogen, zymogen processing
ASJC Classification2700 General Medicine; 1312 Molecular Biology; 1503 Catalysis; 1604 Inorganic Chemistry; 1605 Organic Chemistry; 1606 Physical and Theoretical Chemistry; 1607 Spectroscopy; 1706 Computer Science Applications
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)140
Score sourcejournalList
ScoreMinisterial score = 140.0, 27-03-2020, ArticleFromJournal
Publication indicators Scopus Citations = 0; WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.224; WoS Impact Factor: 2018 = 4.183 (2) - 2018=4.331 (5)
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