Catalytic deficiency of O-GlcNAc transferase leads to X-linked intellectual disability

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 116; no. 30; p. 14961
• Main Authors: Pravata, Veronica M, Muha, Villo, Gundogdu, Mehmet, Ferenbach, Andrew T, Kakade, Poonam S, Vandadi, Vasudha, Wilmes, Ariane C, Borodkin, Vladimir S, Joss, Shelagh, Stavridis, Marios P, van Aalten, Daan M F
• Format: Journal Article
• Language: English
• Published: Washington National Academy of Sciences 23-07-2019
• Subjects: Anaerobes; Catalysis; CheA protein; Chemoreceptors; Chemotaxis; Crystal structure; Domains; Histidine; Histidine kinase; Iron; Kinases; Nitric oxide; Oxygen; Prokaryotes; Receptors; Reductases; Zinc
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1904234116

Many bacteria contain cytoplasmic chemoreceptors that lack sensor domains. Here, we demonstrate that such cytoplasmic receptors found in 8 different bacterial and archaeal phyla genetically couple to metalloproteins related to β-lactamases and nitric oxide reductases. We show that this oxygen-binding di-iron protein (ODP) acts as a sensor for chemotactic responses to both iron and oxygen in the human pathogen Treponema denticola (Td). The ODP di-iron site binds oxygen at high affinity to reversibly form an unusually stable μ-peroxo adduct. Crystal structures of ODP from Td and the thermophile Thermotoga maritima (Tm) in the Fe[III]2-O22−, Zn[II], and apo states display differences in subunit association, conformation, and metal coordination that indicate potential mechanisms for sensing. In reconstituted systems, iron-peroxo ODP destabilizes the phosphorylated form of the receptor-coupled histidine kinase CheA, thereby providing a biochemical link between oxygen sensing and chemotaxis in diverse prokaryotes, including anaerobes of ancient origin.