7W81

Crystal structure of the heme-bound form of the linker-NEAT3 region of IsdH from Staphylococcus aureus

Summary for 7W81

• Entry DOI: 10.2210/pdb7w81/pdb
• Descriptor: Iron-regulated surface determinant protein H, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• Functional Keywords: iron acquisition, antimicrobial, hemoglobin, isd system, staphylococcus aureus, heme, metal transport
• Biological source: Staphylococcus aureus (strain Mu50 / ATCC 700699)
• Total number of polymer chains: 2
• Total formula weight: 43302.54

Authors

Caaveiro, J.M.M.,Vu, N.,Tsumoto, K. (deposition date: 2021-12-07, release date: 2022-10-19, Last modification date: 2023-11-29)

Primary citation

Valenciano-Bellido, S.,Caaveiro, J.M.M.,Morante, K.,Sushko, T.,Nakakido, M.,Nagatoishi, S.,Tsumoto, K.
Structure and role of the linker domain of the iron surface-determinant protein IsdH in heme transportation in Staphylococcus aureus.
J.Biol.Chem., 298:101995-101995, 2022

PubMed Abstract: Staphylococcus aureus is a major cause of deadly nosocomial infections, a severe problem fueled by the steady increase of resistant bacteria. The iron surface determinant (Isd) system is a family of proteins that acquire nutritional iron from the host organism, helping the bacterium to proliferate during infection, and therefore represents a promising antibacterial target. In particular, the surface protein IsdH captures hemoglobin (Hb) and acquires the heme moiety containing the iron atom. Structurally, IsdH comprises three distinctive NEAr-iron Transporter (NEAT) domains connected by linker domains. The objective of this study was to characterize the linker region between NEAT2 and NEAT3 from various biophysical viewpoints and thereby advance our understanding of its role in the molecular mechanism of heme extraction. We demonstrate the linker region contributes to the stability of the bound protein, likely influencing the flexibility and orientation of the NEAT3 domain in its interaction with Hb, but only exerts a modest contribution to the affinity of IsdH for heme. Based on these data, we suggest that the flexible nature of the linker facilitates the precise positioning of NEAT3 to acquire heme. In addition, we also found that residues His45 and His89 of Hb located in the heme transfer route toward IsdH do not play a critical role in the transfer rate-determining step. In conclusion, this study clarifies key elements of the mechanism of heme extraction of human Hb by IsdH, providing key insights into the Isd system and other protein systems containing NEAT domains.

PubMed: 35500652
DOI: 10.1016/j.jbc.2022.101995

Experimental method

X-RAY DIFFRACTION (1.8 Å)