Modulation by nitric oxide of metalloprotein regulatory activities.
In many cells, a nitric oxide (NO) synthase inducible by immunological stimuli produces a sustained flow of NO that lasts a long time. NO is a short-lived molecule but it is a diffusible ligand believed to be capable of reaching distal target sites. Further, several lines of evidence indicate that cysteine-rich motifs of metal-binding proteins, as well as redox-sensitive metal clusters of metalloproteins, are natural sensors of bioradicals like NO. In metalloregulatory proteins, metals are often conveniently located at binding sites and bound to cysteine residues. Accordingly, disruption of the metal-thiolate polymetallic clusters should trigger significant remodelling of the protein structure involved in regulation. We can therefore postulate that the nitrosation reaction occurring at metal centres or cysteine-rich motifs will preclude correct binding to regulatory sites. Several examples are given of metalloregulatory proteins whose metal is bound to thiols and may then become sensitive to NO. Recent observations indicate that in response to NO synthesis, iron regulatory protein, a eukaryotic bifunctional [Fe-S] protein, switches from acting as aconitase to being an RNA-binding regulator, and we suggest that the interplay between NO or a NO-derived molecule and metal clusters at critical allosteric sites may be a crucial component of the cellular response to environmental stress.
Drapier
J C
JC
U 365 INSERM, Section de Recherche, Institut Curie, Paris, France.
Bouton
C
C
D004268:DNA-Binding Proteins / Q000378:metabolism; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D008667:Metalloproteins / Q000378:metabolism*; D008956:Models, Chemical; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism
D004268:DNA-Binding Proteins; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D008667:Metalloproteins; D016601:RNA-Binding Proteins; D009569:Nitric Oxide; D007501:Iron; D019001:Nitric Oxide Synthase