6E4D

Atomic structure of Mycobacterium tuberculosis DppA

Summary for 6E4D

• Entry DOI: 10.2210/pdb6e4d/pdb
• Related: 6E3D
• Descriptor: Periplasmic dipeptide-binding lipoprotein DPPA, VAL-VAL-VAL-ALA (3 entities in total)
• Functional Keywords: heme-binding, periplasmic protein, metal binding protein
• Biological source: Mycobacterium tuberculosis; More
• Total number of polymer chains: 2
• Total formula weight: 55783.95

Authors

Ko, Y.,Mitra, A.,Niederweis, M.,Cingolani, G. (deposition date: 2018-07-17, release date: 2019-09-11, Last modification date: 2023-10-11)

Primary citation

Mitra, A.,Ko, Y.H.,Cingolani, G.,Niederweis, M.
Heme and hemoglobin utilization by Mycobacterium tuberculosis.
Nat Commun, 10:4260-4260, 2019

PubMed 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.

PubMed: 31534126
DOI: 10.1038/s41467-019-12109-5

Experimental method

X-RAY DIFFRACTION (1.252 Å)