dc.contributor.author | Mitra, Avishek | |
dc.contributor.author | Ko, Ying-Hui | |
dc.contributor.author | Cingolani, Gino | |
dc.contributor.author | Niederweis, Michael | |
dc.date.accessioned | 2023-02-16T16:39:58Z | |
dc.date.available | 2023-02-16T16:39:58Z | |
dc.date.issued | 2019-09-18 | |
dc.identifier | oksd_mitra_heme_and_hemoglobin_utilization_2019 | |
dc.identifier.citation | Mitra, A., Ko, Y.-H., Cingolani, G., Niederweis, M. (2019). Heme and hemoglobin utilization by Mycobacterium tuberculosis. Nature Communications, 10(1), 1-14. https://doi.org/10.1038/s41467-019-12109-5 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://hdl.handle.net/11244/337038 | |
dc.description.abstract | Iron is essential for growth of Mycobacterium tuberculosis (Mtb), but most iron in the human body is stored in heme within hemoglobin. Here, we demonstrate that the substrate-binding protein DppA of the inner membrane Dpp transporter is required for heme and hemoglobin utilization by Mtb. The 1.27 Å crystal structure of DppA shows a tetrapeptide bound in the protein core and a large solvent-exposed crevice for heme binding. Mutation of arginine 179 in this cleft eliminates heme binding to DppA and prevents heme utilization by Mtb. The outer membrane proteins PPE36 and PPE62 are also required for heme and hemoglobin utilization, indicating that these pathways converge at the cell surface of Mtb. Albumin, the most abundant blood protein, binds heme specifically and bypasses the requirements for PPE36, PPE62 and Dpp. Thus, our study reveals albumin-dependent and -independent heme uptake pathways, highlighting the importance of iron acquisition from heme for Mtb. | |
dc.format | application/pdf | |
dc.language | en_US | |
dc.publisher | Springer Nature | |
dc.relation.ispartof | Nature Communications, 10 (1) | |
dc.rights | This material has been previously published. In the Oklahoma State University Library's institutional repository this version is made available through the open access principles and the terms of agreement/consent between the author(s) and the publisher. The permission policy on the use, reproduction or distribution of the material falls under fair use for educational, scholarship, and research purposes. Contact Digital Resources and Discovery Services at lib-dls@okstate.edu or 405-744-9161 for further information. | |
dc.subject.mesh | albumins | |
dc.subject.mesh | antigens, bacterial | |
dc.subject.mesh | bacterial proteins | |
dc.subject.mesh | crystallography, x-ray | |
dc.subject.mesh | heme | |
dc.subject.mesh | hemoglobins | |
dc.subject.mesh | humans | |
dc.subject.mesh | iron | |
dc.subject.mesh | Mycobacterium tuberculosis | |
dc.subject.mesh | periplasmic binding proteins | |
dc.subject.mesh | protein binding | |
dc.subject.mesh | protein structure, secondary | |
dc.title | Heme and hemoglobin utilization by Mycobacterium tuberculosis | |
dc.date.updated | 2023-02-15T22:59:47Z | |
dc.note | open access status: Gold OA | |
osu.filename | oksd_mitra_heme_and_hemoglobin_utilization_2019.pdf | |
dc.identifier.doi | 10.1038/s41467-019-12109-5 | |
dc.description.department | Microbiology and Molecular Genetics | |
dc.type.genre | Article | |
dc.type.material | Text | |
dc.subject.keywords | tuberculosis | |
dc.subject.keywords | rare diseases | |
dc.subject.keywords | infectious diseases | |
dc.subject.keywords | underpinning research | |
dc.subject.keywords | normal biological development and functioning | |
dc.subject.keywords | good health and well being | |
dc.identifier.author | ORCID: 0000-0003-0243-2045 (Mitra, Avishek) | |
dc.identifier.essn | 2041-1723 | |