Calcium‐induced structural transitions are central to the folding, function, and processing of serratiopeptidase zymogen into mature form

Author:

Srivastava Vishal1,Bandhu Sheetal1,Mishra Shivam1,Chaudhuri Tapan K.1ORCID

Affiliation:

1. Kusuma School of Biological Sciences Indian Institute of Technology Delhi India

Abstract

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.

Funder

Indian Institute of Technology Delhi

Publisher

Wiley

Reference38 articles.

1. Bacterial secretion systems: an overview;Green ER;Microbiol Spectr,2015

2. The Genus Serratia

3. Serratia Infections: from Military Experiments to Current Practice

4. Friend or foe? A review of the mechanisms that driveSerratiatowards diverse lifestyles

5. Serratia marcescens‐ a rare opportunistic nosocomial pathogen and measures to limit its spread in hospitalized patients;Khanna A;J Clin Diagn Res,2013

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