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

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 syn...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801622/
https://www.ncbi.nlm.nih.gov/pubmed/31557781
http://dx.doi.org/10.3390/ijms20194747
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author 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
author_facet 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
author_sort Lamort, Anne-Sophie
collection PubMed
description 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.
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spelling pubmed-68016222019-10-31 Processing and Maturation of Cathepsin C Zymogen: A Biochemical and Molecular Modeling Analysis 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 Int J Mol Sci Article 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. MDPI 2019-09-25 /pmc/articles/PMC6801622/ /pubmed/31557781 http://dx.doi.org/10.3390/ijms20194747 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Processing and Maturation of Cathepsin C Zymogen: A Biochemical and Molecular Modeling Analysis
title Processing and Maturation of Cathepsin C Zymogen: A Biochemical and Molecular Modeling Analysis
title_full Processing and Maturation of Cathepsin C Zymogen: A Biochemical and Molecular Modeling Analysis
title_fullStr Processing and Maturation of Cathepsin C Zymogen: A Biochemical and Molecular Modeling Analysis
title_full_unstemmed Processing and Maturation of Cathepsin C Zymogen: A Biochemical and Molecular Modeling Analysis
title_short Processing and Maturation of Cathepsin C Zymogen: A Biochemical and Molecular Modeling Analysis
title_sort processing and maturation of cathepsin c zymogen: a biochemical and molecular modeling analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801622/
https://www.ncbi.nlm.nih.gov/pubmed/31557781
http://dx.doi.org/10.3390/ijms20194747
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