Summary for 9O0J
| Entry DOI | 10.2210/pdb9o0j/pdb |
| Descriptor | Membrane protein HtaACR1, PROTOPORPHYRIN IX CONTAINING FE, DI(HYDROXYETHYL)ETHER, ... (6 entities in total) |
| Functional Keywords | cr, complex, transport protein |
| Biological source | Corynebacterium diphtheriae NCTC 13129 |
| Total number of polymer chains | 10 |
| Total formula weight | 194017.85 |
| Authors | Ford, J.,Sawaya, M.R.,Clubb, R.T. (deposition date: 2025-04-02, release date: 2025-09-03, Last modification date: 2025-10-08) |
| Primary citation | Ford, J.,Goring, A.K.,Lee, Y.,Chen, M.,Mahoney, B.J.,Sawaya, M.R.,Shafaat, H.S.,Loo, J.A.,Clubb, R.T. Structural basis of heme scavenging by the ChtA and HtaA hemophores in Corynebacterium diphtheriae. J.Biol.Chem., 301:110633-110633, 2025 Cited by PubMed Abstract: Corynebacterium diphtheriae causes diphtheria, a potentially fatal infectious disease that damages tissues in the upper respiratory tract. In order to proliferate, this pathogen acquires the essential nutrient iron from heme (iron-protoporphyrin IX) primarily found in human hemoglobin (Hb). C. diphtheriae secretes ChtA and HtaA hemophore proteins that bind ferric heme (hemin) via Conserved Region (CR) domains. Here we demonstrate that their CR domains scavenge hemin after it is spontaneously released from Hb, and define the structural basis of hemin binding to ChtA and the N-terminal CR domain from HtaA by determining X-ray crystal structures of their protein-hemin complexes. Resonance Raman and EPR experiments demonstrate that the CR domains from ChtA and HtaA engage in pentacoordinate hemin binding through a conserved iron-tyrosyl linkage, though variations in their hemin pockets alter the way they stabilize the axial tyrosine and mask hemin's metal. The importance of these interactions is probed using isothermal titration calorimetry experiments, which represent the first quantitative assessment of CR-hemin affinity and reveal that ChtA binds hemin via an enthalpically driven process. Hemin partitioning experiments using native mass spectrometry demonstrate that the cohort of CR domains within C. diphtheriae's hemin-uptake system have dissociation constants for hemin between 0.8 to 22 nM, raising the possibility that affinity differences contribute to the directional flow of hemin into the cell. Collectively, the results of this work provide insight into how C. diphtheriae and other pathogenic and commensal corynebacterium species utilize CR domains to scavenge iron rich hemin from their environment. PubMed: 40876592DOI: 10.1016/j.jbc.2025.110633 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.88 Å) |
Structure validation
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