期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 12, 页码 5051-5056出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1009516108
关键词
X-ray crystallography; iron uptake
资金
- Colorado State University, National Institutes of Health, National Institute of Allergy and Infectious Diseases [N01 AI-75320]
- National and California American Lung Association [RG-78755-N]
- National Institutes of Health [AI081161, AI068135, A1078691, AI068413, AI078691, HL077000]
Mycobacterium tuberculosis must import iron from its host for survival, and its siderophore-dependent iron acquisition pathways are well established. Here we demonstrate a newly characterized pathway, whereby M. tuberculosis can use free heme and heme from hemoglobin as an iron source. Significantly, we identified the genomic region, Rv0202c-Rv0207c, responsible for the passage of heme iron across the mycobacterial membrane. Key players of this heme uptake system were characterized including a secreted protein and two transmembrane proteins, all three specific to mycobacteria. Furthermore, the crystal structure of the key heme carrier protein Rv0203 was found to have a unique fold. The discovery of a unique mycobacterial heme acquisition pathway opens new avenues of exploration into mycobacterial therapeutics.
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