Calcium-induced structural transitions are central to the folding, function, and processing of serratiopeptidase zymogen into mature form.
Serratia marcescens
metalloprotease
protein folding
pro‐peptide processing
repeat‐in toxin family
serralysin
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
May 2024
May 2024
Historique:
revised:
05
01
2024
received:
06
11
2023
accepted:
01
02
2024
medline:
3
5
2024
pubmed:
3
5
2024
entrez:
3
5
2024
Statut:
ppublish
Résumé
Serratia marcescens is an emerging health-threatening, gram-negative opportunistic pathogen associated with a wide variety of localized and life-threatening systemic infections. One of the most crucial virulence factors produced by S. marcescens is serratiopeptidase, a 50.2-kDa repeats-in-toxin (RTX) family broad-specificity zinc metalloprotease. RTX family proteins are functionally diverse exoproteins of gram-negative bacteria that exhibit calcium-dependent structural dynamicity and are secreted through a common type-1 secretion system (T1SS) machinery. To evaluate the impact of various divalent ligands on the folding and maturation of serratiopeptidase zymogen, the protein was purified and a series of structural and functional investigations were undertaken. The results indicate that calcium binding to the C-terminal RTX domain acts as a folding switch, triggering a disordered-to-ordered transition in the enzyme's conformation. Further, the auto-processing of the 16-amino acid N-terminal pro-peptide results in the maturation of the enzyme. The binding of calcium ions to serratiopeptidase causes a highly cooperative conformational transition in its structure, which is essential for the enzyme's activation and maturation. This conformational change is accompanied by an increase in solubility and enzymatic activity. For efficient secretion and to minimize intracellular toxicity, the enzyme needs to be in an unfolded extended form. The calcium-rich extracellular environment favors the folding and processing of zymogen into mature serratiopeptidase, i.e., the holo-form required by S. marcescens to establish infections and survive in different environmental niches.
Substances chimiques
Calcium
SY7Q814VUP
Enzyme Precursors
0
serratiopeptidase
NL053ABE4J
Metalloendopeptidases
EC 3.4.24.-
Bacterial Proteins
0
Peptide Hydrolases
EC 3.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1958-1973Subventions
Organisme : IIT Delhi
Informations de copyright
© 2024 Federation of European Biochemical Societies.
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