9BCJ

Molecular basis of hemoglobin binding and heme removal in Corynebacterium diphtheriae.

(2025) Proc Natl Acad Sci U S A 122: e2411833122-e2411833122

• PubMed: 39739808 Search on PubMed
• DOI: https://doi.org/10.1073/pnas.2411833122
• Primary Citation of Related Structures:  
  9BCH, 9BCJ


• PubMed Abstract: 
  

  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 α subunits. Quantitative growth and heme release measurements are compatible with C. diphtheriae acquiring heme passively released from hemoglobin's β 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 β subunit to release heme likely represent a common strategy used by bacterial pathogens to obtain iron during infections.

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Organizational Affiliation: 

Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095.