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Open AccessArticle

Processing and Maturation of Cathepsin C Zymogen: A Biochemical and Molecular Modeling Analysis

1
INSERM UMR-1100, CEPR (Centre d’Etude des Pathologies Respiratoires), 37032 Tours, France
2
Université de Tours, 37032 Tours, France
3
Comprehensive Pneumology Center and Institute for Lung Biology and Disease; University Hospital, Ludwig-Maximilians University of Munich and Helmholtz Center Munich; Member of the German Center for Lung Research, 81377 Munich, Germany
4
Faculty of Chemistry, University of Gdansk, 80-308 Gdansk, Poland
5
CNRS UMR-6270, Normandie Université, Plate-forme PISSARO, 76821 Mont Saint Aignan, France
6
Max Planck Institute of Neurobiology, 82152 Planegg-Martinsried, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(19), 4747; https://doi.org/10.3390/ijms20194747
Received: 19 August 2019 / Revised: 11 September 2019 / Accepted: 18 September 2019 / Published: 25 September 2019
(This article belongs to the Section Biochemistry)
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. View Full-Text
Keywords: Cathepsin C; cysteine cathepsin; zymogen; zymogen processing Cathepsin C; cysteine cathepsin; zymogen; zymogen processing
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MDPI and ACS Style

Lamort, A.-S.; Hamon, Y.; Czaplewski, C.; Gieldon, A.; Seren, S.; Coquet, L.; Lecaille, F.; Lesner, A.; Lalmanach, G.; Gauthier, F.; Jenne, D.; Korkmaz, B. Processing and Maturation of Cathepsin C Zymogen: A Biochemical and Molecular Modeling Analysis. Int. J. Mol. Sci. 2019, 20, 4747. https://doi.org/10.3390/ijms20194747

AMA Style

Lamort A-S, Hamon Y, Czaplewski C, Gieldon A, Seren S, Coquet L, Lecaille F, Lesner A, Lalmanach G, Gauthier F, Jenne D, Korkmaz B. Processing and Maturation of Cathepsin C Zymogen: A Biochemical and Molecular Modeling Analysis. International Journal of Molecular Sciences. 2019; 20(19):4747. https://doi.org/10.3390/ijms20194747

Chicago/Turabian Style

Lamort, Anne-Sophie; Hamon, Yveline; Czaplewski, Cezary; Gieldon, Artur; Seren, Seda; Coquet, Laurent; Lecaille, Fabien; Lesner, Adam; Lalmanach, Gilles; Gauthier, Francis; Jenne, Dieter; Korkmaz, Brice. 2019. "Processing and Maturation of Cathepsin C Zymogen: A Biochemical and Molecular Modeling Analysis" Int. J. Mol. Sci. 20, no. 19: 4747. https://doi.org/10.3390/ijms20194747

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