7w81
Crystal structure of the heme-bound form of the linker-NEAT3 region of IsdH from Staphylococcus aureusCrystal structure of the heme-bound form of the linker-NEAT3 region of IsdH from Staphylococcus aureus
Structural highlights
FunctionISDH_STAAM Binds human plasma haptoglobin-hemoglobin complexes, haptoglobin and hemoglobin. Binds haptoglobin-hemoglobin complexes with significantly higher affinity than haptoglobin alone (By similarity). Publication Abstract from PubMedStaphylococcus 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. Structure and role of the linker domain of the iron surface-determinant protein IsdH in heme transportation in Staphylococcus aureus.,Valenciano-Bellido S, Caaveiro JMM, Morante K, Sushko T, Nakakido M, Nagatoishi S, Tsumoto K J Biol Chem. 2022 Jun;298(6):101995. doi: 10.1016/j.jbc.2022.101995. Epub 2022, Apr 29. PMID:35500652[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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