9S4F

Human carboxyhemoglobin bound to Staphylococcus aureus IsdH-N2N3 - 2IsdH:Hbdim complex - 3DVA component 4 right tail

Summary for 9S4F

• Entry DOI: 10.2210/pdb9s4f/pdb
• Related: 9S3P
• EMDB information: 54563
• Descriptor: Hemoglobin subunit alpha, Hemoglobin subunit beta, Iron-regulated surface determinant protein H, ... (4 entities in total)
• Functional Keywords: iron acquisition, hemophore, hemoglobin, neat domain, metal transport
• Biological source: Staphylococcus aureus; More
• Total number of polymer chains: 4
• Total formula weight: 115075.54

Authors

Buoli Comani, V.,De Bei, O.,Gragera, M.,Luisi, B.F.,Bettati, S. (deposition date: 2025-07-28, release date: 2025-11-12, Last modification date: 2025-12-10)

Primary citation

Buoli Comani, V.,De Bei, O.,Pancrazi, F.,Gragera, M.,Paris, G.,Marchetti, M.,Campanini, B.,Ronda, L.,Luisi, B.F.,Faggiano, S.,Bizzarri, A.R.,Bettati, S.
Hemoglobin receptor redundancy in Staphylococcus aureus : molecular flexibility as a determinant of divergent hemophore activity.
J Struct Biol X, 12:100138-100138, 2025

PubMed Abstract: To overcome iron limitation in the host, exploits sophisticated mechanisms to acquire this essential nutrient, particularly from hemoglobin (Hb). The bacterial hemophores IsdH and IsdB play key roles in binding Hb and extracting heme, but the structural and mechanistic differences underlying their individual contributions remain poorly defined. In this study, we dissected the molecular mechanisms by which IsdH engages Hb and mediates heme extraction, using cryo-electron microscopy, biochemical assays, and single-molecule force spectroscopy. Our structural analyses revealed pronounced conformational heterogeneity within IsdH:Hb complexes, highlighting marked flexibility in the heme-binding domain of IsdH, likely underlying its distinct functional behavior. This plasticity contrasts with the more rigid architecture of IsdB. The flexibility observed in IsdH correlates with our biochemical and biophysical findings, supporting its functional relevance. Unlike IsdB, IsdH does not display selectivity for α- or β-Hb chains and shows reduced involvement of the heme-binding domain in Hb recognition. It also follows a distinct kinetic mechanism for heme capture, which begins upon binding but proceeds more slowly than in IsdB. Finally, IsdH does not exhibit the catch bond-like behavior characteristic of IsdB, suggesting it may act in different physiological niches or conditions. Collectively, these findings highlight a distinct mode of Hb engagement by IsdH, shaped by its dynamic and flexible architecture, and provide mechanistic insight into the diversity of iron acquisition strategies employed by .

PubMed: 41321687
DOI: 10.1016/j.yjsbx.2025.100138

Experimental method

ELECTRON MICROSCOPY (4.2 Å)