7PCQ

Human carboxyhemoglobin bound to Staphylococcus aureus hemophore IsdB - 1:1 complex

7PCQ の概要

• エントリーDOI: 10.2210/pdb7pcq/pdb
• EMDBエントリー: 13325
• 分子名称: Hemoglobin subunit alpha, Hemoglobin subunit beta, Iron-regulated surface determinant protein B, ... (4 entities in total)
• 機能のキーワード: iron acquisition, hemophore, hemoglobin, neat domain, metal transport
• 由来する生物種: Staphylococcus aureus subsp. aureus MW2; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 107940.18

構造登録者

De Bei, O.,Gianquinto, E.,Chirgadze, D.Y.,Hardwick, S.W.,Spyrakis, F.,Luisi, B.F.,Campanini, B. (登録日: 2021-08-03, 公開日: 2022-04-13, 最終更新日: 2024-07-17)

主引用文献

De Bei, O.,Marchetti, M.,Ronda, L.,Gianquinto, E.,Lazzarato, L.,Chirgadze, D.Y.,Hardwick, S.W.,Cooper, L.R.,Spyrakis, F.,Luisi, B.F.,Campanini, B.,Bettati, S.
Cryo-EM structures of staphylococcal IsdB bound to human hemoglobin reveal the process of heme extraction.
Proc.Natl.Acad.Sci.USA, 119:e2116708119-e2116708119, 2022

PubMed Abstract: Iron surface determinant B (IsdB) is a hemoglobin (Hb) receptor essential for hemic iron acquisition by Staphylococcus aureus. Heme transfer to IsdB is possible from oxidized Hb (metHb), but inefficient from Hb either bound to oxygen (oxyHb) or bound to carbon monoxide (HbCO), and encompasses a sequence of structural events that are currently poorly understood. By single-particle cryo-electron microscopy, we determined the structure of two IsdB:Hb complexes, representing key species along the heme extraction pathway. The IsdB:HbCO structure, at 2.9-Å resolution, provides a snapshot of the preextraction complex. In this early stage of IsdB:Hb interaction, the hemophore binds to the β-subunits of the Hb tetramer, exploiting a folding-upon-binding mechanism that is likely triggered by a cis/trans isomerization of Pro173. Binding of IsdB to α-subunits occurs upon dissociation of the Hb tetramer into α/β dimers. The structure of the IsdB:metHb complex reveals the final step of the extraction process, where heme transfer to IsdB is completed. The stability of the complex, both before and after heme transfer from Hb to IsdB, is influenced by isomerization of Pro173. These results greatly enhance current understanding of structural and dynamic aspects of the heme extraction mechanism by IsdB and provide insight into the interactions that stabilize the complex before the heme transfer event. This information will support future efforts to identify inhibitors of heme acquisition by S. aureus by interfering with IsdB:Hb complex formation.

PubMed: 35357971
DOI: 10.1073/pnas.2116708119

実験手法

ELECTRON MICROSCOPY (3.62 Å)