Open AccessCryo-EM structures of staphylococcal IsdB bound to human hemoglobin reveal the process of heme extraction
Author(s) -
Omar De Bei,
Marialaura Marchetti,
Luca Ronda,
Eleonora Gianquinto,
Loretta Lazzarato,
Dimitri Y. Chirgadze,
Steven W. Hardwick,
Lee R. Cooper,
Francesca Spyrakis,
B.F. Luisi,
Barbara Campanini,
Stefano Bettati
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2116708119
Subject(s) - heme , hemoglobin , staphylococcus aureus , chemistry , biochemistry , bacteria , biology , enzyme , genetics
Significance During infection, the human pathogenStaphylococcus aureus expresses a surface-exposed receptor, Iron surface determinant B (IsdB), that captures free human hemoglobin (Hb) and removes heme to retrieve iron, an essential nutrient for bacterial proliferation inside the host. Using single-particle cryo-electron microscopy, we solved the structure of two complexes between Hb and IsdB that represent snapshots of the initial interaction, where heme is still bound to Hb, and the final complex after completion of heme extraction. The structural and dynamic details unlocked through these structures will boost the design of inhibitors of IsdB:Hb interaction that might work as innovative antimicrobials.