Structural Basis and Mechanism of a Unique Haemophore in the Haem‐Iron Acquisition by Riemerella anatipestifer

Structural Basis and Mechanism of a Unique Haemophore in the Haem‐Iron Acquisition by Riemerella anatipestifer

Abstract Several bacterial pathogens employ haemophores to scavenge haem from host haemoprotein to obtain an iron source. However, no homologues of well‐characterized haemophores are found in Riemerella anatipestifer, a bacterium belonging to the order Flavobacteriales that encodes haem uptake syste...

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Main Authors: Mengying Wang, Dandan Zhang, Xiu Tian, Jiangyang Tong, Yizhou Yao, Mingshu Wang, Dekang Zhu, Renyong Jia, Shun Chen, Xinxin Zhao, Shaqiu Zhang, Juan Huang, Xumin Ou, Bin Tian, Di Sun, Yu He, Zhen Wu, Songying Ouyang, Mafeng Liu, Anchun Cheng
Format: Article
Language:English
Published: Wiley 2025-04-01
Series:Advanced Science
Subjects:
haem
haemophore
iron
Riemerella anatipestifer
Online Access:https://doi.org/10.1002/advs.202412202
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Summary:Abstract Several bacterial pathogens employ haemophores to scavenge haem from host haemoprotein to obtain an iron source. However, no homologues of well‐characterized haemophores are found in Riemerella anatipestifer, a bacterium belonging to the order Flavobacteriales that encodes haem uptake systems. Herein, a unique haemophore RhuH is characterized in this bacterium. R. anatipestifer used RhuH to grow when duck hemoglobin serves as the sole iron resource. RhuH is secreted as a component of outer membrane vesicles. Recombinant RhuH exhibited a high binding affinity for haem (Kd of 3.44 × 10−11 m) and can extract haem from duck hemoglobin. X‐ray crystallography elucidated the 3D structure of RhuH at 2.85 Å resolution, showing a dimeric conformation with each monomer exhibiting a unique structure. Structure modeling of RhuH‐haem, coupled with mutagenesis, haemin utilization, and binding affinity assays, show that haem is captured in the β‐barrel–like region, displaying the classic iron coordination. The RhuH homologues are predominantly distributed in Weeksellaceae and Flavobacteriaceae. Finally, the homologues of RhuH in Riemerella columbina, Flavobacterium columnare, and Flavobacterium soli are used as a proof of concept, demonstrating that these homologues exhibit conserved structures and functions.
ISSN:2198-3844

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