The Mycobacterium tuberculosis Secreted Protein Rv0203 Transfers Heme to Membrane Proteins MmpL3 and MmpL11
| Autor: | Celia W. Goulding, Christine A. Harmston, Amanda B. Graves, Nicholas Chim, Heidi Contreras, Angelina Iniguez, Cedric P. Owens, Matthew D. Liptak |
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| Rok vydání: | 2013 |
| Předmět: |
Hemeproteins
Hemeprotein Metalloporphyrins Molecular Sequence Data Heme Plasma protein binding Models Biological Biochemistry Mycobacterium tuberculosis chemistry.chemical_compound Bacterial Proteins Humans Tuberculosis Amino Acid Sequence Molecular Biology Binding Sites Sequence Homology Amino Acid biology Membrane transport protein Circular Dichroism Electron Spin Resonance Spectroscopy Membrane Proteins Membrane Transport Proteins Biological Transport Cell Biology Periplasmic space biology.organism_classification Recombinant Proteins Kinetics Membrane protein chemistry Enzymology biology.protein Electrophoresis Polyacrylamide Gel Carrier Proteins Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 288:21714-21728 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m113.453076 |
| Popis: | Mycobacterium tuberculosis is the causative agent of tuberculosis, which is becoming an increasingly global public health problem due to the rise of drug-resistant strains. While residing in the human host, M. tuberculosis needs to acquire iron for its survival. M. tuberculosis has two iron uptake mechanisms, one that utilizes non-heme iron and another that taps into the vast host heme-iron pool. To date, proteins known to be involved in mycobacterial heme uptake are Rv0203, MmpL3, and MmpL11. Whereas Rv0203 transports heme across the bacterial periplasm or scavenges heme from host heme proteins, MmpL3 and MmpL11 are thought to transport heme across the membrane. In this work, we characterize the heme-binding properties of the predicted extracellular soluble E1 domains of both MmpL3 and MmpL11 utilizing absorption, electron paramagnetic resonance, and magnetic circular dichroism spectroscopic methods. Furthermore, we demonstrate that Rv0203 transfers heme to both MmpL3-E1 and MmpL11-E1 domains at a rate faster than passive heme dissociation from Rv0203. This work elucidates a key step in the mycobacterial uptake of heme, and it may be useful in the development of anti-tuberculosis drugs targeting this pathway. |
| Databáze: | OpenAIRE |
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