HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Characterization of a Mycobacterium tuberculosis nanocompartment and its potential cargo proteins.

Abstract
Mycobacterium tuberculosis has evolved various mechanisms by which the bacterium can maintain homeostasis under numerous environmental assaults generated by the host immune response. M. tuberculosis harbors enzymes involved in the oxidative stress response that aid in survival during the production of reactive oxygen species in activated macrophages. Previous studies have shown that a dye-decolorizing peroxidase (DyP) is encapsulated by a bacterial nanocompartment, encapsulin (Enc), whereby packaged DyP interacts with Enc via a unique C-terminal extension. M. tuberculosis also harbors an encapsulin homolog (CFP-29, Mt-Enc), within an operon with M. tuberculosis DyP (Mt-DyP), which contains a C-terminal extension. Together these observations suggest that Mt-DyP interacts with Mt-Enc. Furthermore, it has been suggested that DyPs may function as either a heme-dependent peroxidase or a deferrochelatase. Like Mt-DyP, M. tuberculosis iron storage ferritin protein, Mt-BfrB, and an M. tuberculosis protein involved in folate biosynthesis, 7,8-dihydroneopterin aldolase (Mt-FolB), have C-terminal tails that could also interact with Mt-Enc. For the first time, we show by co-purification and electron microscopy that mycobacteria via Mt-Enc can encapsulate Mt-DyP, Mt-BfrB, and Mt-FolB. Functional studies of free or encapsulated proteins demonstrate that they retain their enzymatic activity within the Mt-Enc nanocompartment. Mt-DyP, Mt-FolB, and Mt-BfrB all have antioxidant properties, suggesting that if these proteins are encapsulated by Mt-Enc, then this nanocage may play a role in the M. tuberculosis oxidative stress response. This report provides initial structural and biochemical clues regarding the molecular mechanisms that utilize compartmentalization by which the mycobacterial cell may aid in detoxification of the local environment to ensure long term survival.
AuthorsHeidi Contreras, Matthew S Joens, Lisa M McMath, Vincent P Le, Michael V Tullius, Jaqueline M Kimmey, Neda Bionghi, Marcus A Horwitz, James A J Fitzpatrick, Celia W Goulding
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 289 Issue 26 Pg. 18279-89 (Jun 27 2014) ISSN: 1083-351X [Electronic] United States
PMID24855650 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Chemical References
  • Bacterial Proteins
  • Peroxidase
  • Aldehyde-Lyases
  • dihydroneopterin aldolase
Topics
  • Aldehyde-Lyases (genetics, metabolism)
  • Bacterial Proteins (genetics, metabolism)
  • Mycobacterium tuberculosis (enzymology, genetics, metabolism)
  • Organelles (genetics, metabolism)
  • Peroxidase (genetics, metabolism)
  • Protein Binding

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: