Heme is an effector molecule for iron-dependent degradation of the bacterial iron response regulator (Irr) protein
AUTOR(ES)
Qi, Zhenhao
FONTE
The National Academy of Sciences
RESUMO
The bacterial iron response regulator (Irr) protein mediates iron-dependent regulation of heme biosynthesis. Pulse–chase and immunoprecipitation experiments showed that Irr degraded in response to 6 μM iron with a half-life of ≈30 min and that this regulated stability was the principal determinant of control by iron. Irr contains a heme regulatory motif (HRM) near its amino terminus. A role for heme in regulation was implicated by the retention of Irr in heme synthesis mutants in the presence of iron. Addition of heme to low iron (0.3 μM) cultures was sufficient for the disappearance of Irr in cells of the wild-type and heme mutant strains. Spectral and binding analyses of purified recombinant Irr showed that the protein bound heme with high affinity and caused a blue shift in the absorption spectrum of heme to a shorter wavelength. A Cys29 → Ala substitution within the HRM of Irr (IrrC29A) abrogated both high affinity binding to heme and the spectral blue shift. In vivo turnover experiments showed that, unlike wild-type Irr, IrrC29A was stable in the presence of iron. We conclude that iron-dependent degradation of Irr involves direct binding of heme to the protein at the HRM. The findings implicate a regulatory role for heme in protein degradation and provide direct evidence for a functional HRM in a prokaryote.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=23899Documentos Relacionados
- Iron-dependent oxidation, ubiquitination, and degradation of iron regulatory protein 2: Implications for degradation of oxidized proteins
- A Phosphomimetic Mutation at Ser-138 Renders Iron Regulatory Protein 1 Sensitive to Iron-Dependent Degradation
- An Iron-Binding Protein, Dpr, from Streptococcus mutans Prevents Iron-Dependent Hydroxyl Radical Formation In Vitro
- Iron-Dependent Transcription of the frpB Gene of Helicobacter pylori Is Controlled by the Fur Repressor Protein
- Iron-Dependent Production of Hydroxamate by Sodium-Dependent Azotobacter chroococcum