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Structural basis for the recognition of human hemoglobin by the heme-acquisition protein Shr from Streptococcus pyogenes.

ABSTRACT: In Gram-positive bacteria, sophisticated machineries to acquire the heme group of hemoglobin (Hb) have evolved to extract the precious iron atom contained in it. In the human pathogen Streptococcus pyogenes, the Shr protein is a key component of this machinery. Herein we present the crystal structure of hemoglobin-interacting domain 2 (HID2) of Shr bound to Hb. HID2 interacts with both, the protein and heme portions of Hb, explaining the specificity of HID2 for the heme-bound form of Hb, but not its heme-depleted form. Further mutational analysis shows little tolerance of HID2 to interfacial mutations, suggesting that its interaction surface with Hb could be a suitable candidate to develop efficient inhibitors abrogating the binding of Shr to Hb.

SUBMITTER: Senoo A

PROVIDER: S-EPMC10912661 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Structural basis for the recognition of human hemoglobin by the heme-acquisition protein Shr from Streptococcus pyogenes.

Senoo Akinobu A Hoshino Masato M Shiomi Toshiki T Nakakido Makoto M Nagatoishi Satoru S Kuroda Daisuke D Nakagawa Ichiro I Tame Jeremy R H JRH Caaveiro Jose M M JMM Tsumoto Kouhei K

Scientific reports 20240305 1

In Gram-positive bacteria, sophisticated machineries to acquire the heme group of hemoglobin (Hb) have evolved to extract the precious iron atom contained in it. In the human pathogen Streptococcus pyogenes, the Shr protein is a key component of this machinery. Herein we present the crystal structure of hemoglobin-interacting domain 2 (HID2) of Shr bound to Hb. HID2 interacts with both, the protein and heme portions of Hb, explaining the specificity of HID2 for the heme-bound form of Hb, but not ...[more]

PMID: 38438508

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The surface protein Shr of Streptococcus pyogenes binds heme and transfers it to the streptococcal heme-binding protein Shp.

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The <i>Streptococcus pyogenes</i> Shr protein captures human hemoglobin using two structurally unique binding domains.

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The Shr receptor from <i>Streptococcus pyogenes</i> uses a cap and release mechanism to acquire heme-iron from human hemoglobin.

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2014-09-16 | GSE61415 | GEO

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CRISPR inhibition of prophage acquisition in Streptococcus pyogenes.

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Identification and characterization of HtsA, a second heme-binding protein made by Streptococcus pyogenes.

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