8DOV

Crystal structure of the Shr Hemoglobin Interacting Domain 2 (HID2) in complex with Hemoglobin

Summary for 8DOV

• Entry DOI: 10.2210/pdb8dov/pdb
• Descriptor: Hemoglobin subunit alpha, Hemoglobin subunit beta, Heme-binding protein Shr, ... (6 entities in total)
• Functional Keywords: duf1533, hemoglobin, heme, hid, complex, beta-sandwich, globin, shr, transport protein
• Biological source: Streptococcus pyogenes; More
• Total number of polymer chains: 11
• Total formula weight: 166414.19

Authors

Macdonald, R.,Mahoney, B.J.,Cascio, D.,Clubb, R.T. (deposition date: 2022-07-14, release date: 2023-01-25, Last modification date: 2023-10-25)

Primary citation

Macdonald, R.,Mahoney, B.J.,Soule, J.,Goring, A.K.,Ford, J.,Loo, J.A.,Cascio, D.,Clubb, R.T.
The Shr receptor from Streptococcus pyogenes uses a cap and release mechanism to acquire heme-iron from human hemoglobin.
Proc.Natl.Acad.Sci.USA, 120:e2211939120-e2211939120, 2023

PubMed Abstract: (group A ) is a clinically important microbial pathogen that requires iron in order to proliferate. During infections, uses the surface displayed Shr receptor to capture human hemoglobin (Hb) and acquires its iron-laden heme molecules. Through a poorly understood mechanism, Shr engages Hb via two structurally unique N-terminal Hb-interacting domains (HID1 and HID2) which facilitate heme transfer to proximal NEAr Transporter (NEAT) domains. Based on the results of X-ray crystallography, small angle X-ray scattering, NMR spectroscopy, native mass spectrometry, and heme transfer experiments, we propose that Shr utilizes a "cap and release" mechanism to gather heme from Hb. In the mechanism, Shr uses the HID1 and HID2 modules to preferentially recognize only heme-loaded forms of Hb by contacting the edges of its protoporphyrin rings. Heme transfer is enabled by significant receptor dynamics within the Shr-Hb complex which function to transiently uncap HID1 from the heme bound to Hb's β subunit, enabling the gated release of its relatively weakly bound heme molecule and subsequent capture by Shr's NEAT domains. These dynamics may maximize the efficiency of heme scavenging by , enabling it to preferentially recognize and remove heme from only heme-loaded forms of Hb that contain iron.

PubMed: 36693107
DOI: 10.1073/pnas.2211939120

Experimental method

X-RAY DIFFRACTION (2.1 Å)