9BCJ

Crystal structure of human hemoglobin in complex with the HbpA receptor from Corynebacterium diphtheriae

Summary for 9BCJ

• Entry DOI: 10.2210/pdb9bcj/pdb
• Related: 9BCH
• Descriptor: Hemoglobin subunit alpha, Hemoglobin subunit beta, Membrane protein, ... (7 entities in total)
• Functional Keywords: complex, hemoglobin, heme, beta-sandwich, protein binding
• Biological source: Corynebacterium diphtheriae NCTC 13129; More
• Total number of polymer chains: 3
• Total formula weight: 54563.29

Authors

Mahoney, B.J.,Cascio, D.,Clubb, R.T. (deposition date: 2024-04-09, release date: 2025-01-08)

Primary citation

Mahoney, B.J.,Lyman, L.R.,Ford, J.,Soule, J.,Cheung, N.A.,Goring, A.K.,Ellis-Guardiola, K.,Collazo, M.J.,Cascio, D.,Ton-That, H.,Schmitt, M.P.,Clubb, R.T.
Molecular basis of hemoglobin binding and heme removal in Corynebacterium diphtheriae.
Proc.Natl.Acad.Sci.USA, 122:e2411833122-e2411833122, 2025

PubMed Abstract: To successfully mount infections, nearly all bacterial pathogens must acquire iron, a key metal cofactor that primarily resides within human hemoglobin. 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 selectively captures iron-loaded hemoglobin by partially ensconcing the heme molecules of its α subunits. Quantitative growth and heme release measurements are compatible with acquiring heme passively released from hemoglobin's β subunits. We propose a model in which HbpA and heme-binding receptors collectively function on the 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.

PubMed: 39739808
DOI: 10.1073/pnas.2411833122

Experimental method

X-RAY DIFFRACTION (1.691 Å)