title: Interaction between the bacterial iron response regulator and ferrochelatase mediates genetic control of heme biosynthesis.
abstract: The heme biosynthetic pathway culminates with the insertion of iron into protoporphyrin catalyzed by ferrochelatase. The Bradyrhizobium japonicum iron response regulator (Irr) protein represses the pathway at an early step under iron limitation to prevent protoporphyrin synthesis from exceeding iron availability. Here, we show that Irr interacts directly with ferrochelatase and responds to iron via the status of heme and protoporphyrin localized at the site of heme synthesis. In the presence of iron, ferrochelatase inactivates Irr, followed by heme-dependent Irr degradation to derepress the pathway. Under iron limitation, protoporphyrin relieves the inhibition of Irr by ferrochelatase, probably by promoting protein dissociation, allowing genetic repression. Thus, metabolic control of the heme pathway involves a regulatory function of a biosynthetic enzyme to affect gene expression. Furthermore, heme can serve as a signaling molecule without accumulating freely in cells.
authors.affiliation: Department of Biochemistry, 140 Farber Hall, The State University of New York at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Zhenhao
authors.initials: Z
authors.lastname: Qi
authors.forename: Mark R
authors.initials: MR
authors.lastname: O'Brian
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D020369:Bradyrhizobium / Q000235:genetics* / Q000378:metabolism*; D005294:Ferrochelatase / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006418:Heme / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D014157:Transcription Factors; C114259:iron response regulator protein, Bacteria; D006418:Heme; D005294:Ferrochelatase