PMID- 24855650 OWN - NLM STAT- MEDLINE DCOM- 20141016 LR - 20240321 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 289 IP - 26 DP - 2014 Jun 27 TI - Characterization of a Mycobacterium tuberculosis nanocompartment and its potential cargo proteins. PG - 18279-89 LID - 10.1074/jbc.M114.570119 [doi] AB - 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. CI - (c) 2014 by The American Society for Biochemistry and Molecular Biology, Inc. FAU - Contreras, Heidi AU - Contreras H AD - From the Departments of Molecular Biology and Biochemistry and. FAU - Joens, Matthew S AU - Joens MS AD - the Waitt Advanced Biophotonics Center, Salk Institute for Biological Studies, La Jolla, California 92037, and. FAU - McMath, Lisa M AU - McMath LM AD - From the Departments of Molecular Biology and Biochemistry and. FAU - Le, Vincent P AU - Le VP AD - From the Departments of Molecular Biology and Biochemistry and. FAU - Tullius, Michael V AU - Tullius MV AD - the Division of Infectious Diseases, Department of Medicine, School of Medicine, UCLA, Los Angeles, California 90095. FAU - Kimmey, Jaqueline M AU - Kimmey JM AD - the Division of Infectious Diseases, Department of Medicine, School of Medicine, UCLA, Los Angeles, California 90095. FAU - Bionghi, Neda AU - Bionghi N AD - the Division of Infectious Diseases, Department of Medicine, School of Medicine, UCLA, Los Angeles, California 90095. FAU - Horwitz, Marcus A AU - Horwitz MA AD - the Division of Infectious Diseases, Department of Medicine, School of Medicine, UCLA, Los Angeles, California 90095. FAU - Fitzpatrick, James A J AU - Fitzpatrick JA AD - the Waitt Advanced Biophotonics Center, Salk Institute for Biological Studies, La Jolla, California 92037, and. FAU - Goulding, Celia W AU - Goulding CW AD - From the Departments of Molecular Biology and Biochemistry and Pharmaceutical Sciences, University of California, Irvine, California 92697, celia.goulding@uci.edu. LA - eng GR - GM101945/GM/NIGMS NIH HHS/United States GR - R01 AI081161/AI/NIAID NIH HHS/United States GR - AI078691/AI/NIAID NIH HHS/United States GR - F31 GM101945/GM/NIGMS NIH HHS/United States GR - F31 AI078691/AI/NIAID NIH HHS/United States GR - R01 AI068413/AI/NIAID NIH HHS/United States GR - AI081161/AI/NIAID NIH HHS/United States GR - T35 HL007616/HL/NHLBI NIH HHS/United States GR - AI095208/AI/NIAID NIH HHS/United States GR - AI068413/AI/NIAID NIH HHS/United States GR - P01 AI095208/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140522 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Bacterial Proteins) RN - EC 1.11.1.7 (Peroxidase) RN - EC 4.1.2.- (Aldehyde-Lyases) RN - EC 4.1.2.25 (dihydroneopterin aldolase) SB - IM MH - Aldehyde-Lyases/genetics/*metabolism MH - Bacterial Proteins/genetics/*metabolism MH - Mycobacterium tuberculosis/*enzymology/genetics/metabolism MH - Organelles/genetics/*metabolism MH - Peroxidase/genetics/*metabolism MH - Protein Binding PMC - PMC4140288 OTO - NOTNLM OT - Electron Microscopy (EM) OT - Mycobacterium tuberculosis OT - Nanocompartments OT - Oxidative Stress OT - Protein Self-assembly OT - Protein-Protein Interaction EDAT- 2014/05/24 06:00 MHDA- 2014/10/17 06:00 PMCR- 2015/06/27 CRDT- 2014/05/24 06:00 PHST- 2014/05/24 06:00 [entrez] PHST- 2014/05/24 06:00 [pubmed] PHST- 2014/10/17 06:00 [medline] PHST- 2015/06/27 00:00 [pmc-release] AID - S0021-9258(20)40537-X [pii] AID - M114.570119 [pii] AID - 10.1074/jbc.M114.570119 [doi] PST - ppublish SO - J Biol Chem. 2014 Jun 27;289(26):18279-89. doi: 10.1074/jbc.M114.570119. Epub 2014 May 22.