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-Structure paper
| タイトル | Refining the mechanism of heme acquisition from free hemoglobin by IsdH. |
|---|---|
| ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 123, Issue 20, Page e2601134123, Year 2026 |
| 掲載日 | 2026年5月19日 |
著者 | Valeria Buoli Comani / Omar De Bei / Giulia Paris / Marialaura Marchetti / Francesca Pancrazi / Barbara Campanini / Luca Ronda / Ben F Luisi / Serena Faggiano / Anna Rita Bizzarri / Stefano Bettati / ![]() |
| PubMed 要旨 | is a human pathogen whose virulence depends on iron acquisition. The bacterium expresses the hemophores IsdB and IsdH that enable heme capture from host hemoglobin (Hb). Unlike IsdB, IsdH can bind ... is a human pathogen whose virulence depends on iron acquisition. The bacterium expresses the hemophores IsdB and IsdH that enable heme capture from host hemoglobin (Hb). Unlike IsdB, IsdH can bind both free Hb and Hb:haptoglobin (Hb:Hp) complexes. Here, we present a comprehensive structural analysis of full-length IsdH in complex with free Hb, overcoming the limitations of previous studies based on truncated IsdH constructs. Cryo-EM revealed a previously unobserved oligomeric state and a unique binding pose of the N-terminal Hb-binding domain, likely representing the initial step of Hb engagement. Time-resolved and single-molecule force spectroscopy experiments delineated the sequential steps and mechanical aspects of Hb binding and heme extraction. Together, these findings provide an integrated structural and functional view of the IsdH-Hb interaction in the absence of Hp, as may occur during hemolysis, and offer insights into heme scavenging and potential avenues for therapeutic inhibition. |
リンク | Proc Natl Acad Sci U S A / PubMed:42113987 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.14 - 7.29 Å |
| 構造データ | EMDB-55389, PDB-9szw: ![]() EMDB-55478: Human carboxyhemoglobin bound to full-length Staphylococcus aureus IsdH - 1IsdH:2Hbdim complex |
| 化合物 | ![]() ChemComp-HEM: |
| 由来 |
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キーワード | METAL TRANSPORT / Iron acquisition / Hemophore / Hemoglobin / NEAT domain |
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homo sapiens (ヒト)
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