Molecular basis of hemoglobin binding and heme removal in Corynebacterium diphtheriae

• 成果类型: Article
• 署名作者: Mahoney, Brendan J.; Lyman, Lindsey R.; Ford, Jordan; Soule, Jess; Cheung, Nicole A.; Goring, Andrew K.; Ellis-Guardiola, Kat; Collazo, Michael J.; Cascio, Duilio; Ton-That, Hung; Schmitt, Michael P.; Clubb, Robert T.
• 署名单位: University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; US Food & Drug Administration (FDA); Center for Biologics Evaluation & Research (CBER); University of California System; University of California Los Angeles; University of California System; University of California Los Angeles
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13181
• DOI: 10.1073/pnas.2411833122
• 发表日期: 2025-01-07
• 关键词: nmr structure determination; host iron sources; xplor-nih; acquisition; receptor; identification; siderophore; expression; dtxr; isdh

摘要

To successfully mount infections, nearly all bacterial pathogens must acquire iron, a key metal cofactor that primarily resides within human hemoglobin. Corynebacterium diphtheriae causes the life- threatening respiratory disease diphtheria and captures hemoglobin for iron scavenging using the surface- displayed receptor HbpA. Here, we show using X- ray crystallography, NMR, and in situ binding measurements that C. diphtheriae selectively captures iron- loaded hemoglobin by partially ensconcing the heme molecules of its alpha subunits. Quantitative growth and heme release measurements are compatible with C. diphtheriae acquiring heme passively released from hemoglobin's beta subunits. We propose a model in which HbpA and heme- binding receptors collectively function on the C. diphtheriae surface to capture hemoglobin and its spontaneously released heme. Acquisition mechanisms that exploit the propensity of hemoglobin's beta subunit to release heme likely represent a common strategy used by bacterial pathogens to obtain iron during infections.