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Science 6 August 1993:
Vol. 261. no. 5122, pp. 715 - 725
DOI: 10.1126/science.8342038
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Articles

Science, Vol 261, Issue 5122, 715-725
Copyright © 1993 by American Association for the Advancement of Science

articles

Transition metals in control of gene expression

TV O'Halloran

Department of Chemistry, Northwestern University, Evanston, IL 60208-3113.

Metalloproteins play structural and catalytic roles in gene expression. The metalloregulatory proteins are a subclass that exerts metal-responsive control of genes involved in respiration, metabolism, and metal-specific homeostasis or stress-response systems, such as iron uptake and storage, copper efflux, and mercury detoxification. Two allosteric mechanisms for control of gene expression were first discovered in metalloregulatory systems: an iron-responsive translational control mechanism for ferritin production and a mercury-responsive DNA-distortion mechanism for transcriptional control of detoxification genes. These otherwise unrelated mechanisms give rise to a rapid physiological response when metal ion concentrations exceed a dangerous threshold. Molecular recognition in these allosteric metal ion receptors is achieved through atypical coordination geometries, cluster formation, or complexes with prosthetic groups, such as sulfide and heme. Thus, many of the inorganic assemblies that otherwise buttress the structure of biopolymers or catalyze substrate transformation in active sites of enzymes have also been adapted to serve sensor functions in the metalloregulatory proteins. Mechanistic studies of these metal-sensor protein interactions are providing new insights into fundamental aspects of inorganic chemistry, molecular biology, and cellular physiology.


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Bioinorganic chemistry: a maturing frontier.
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   PDF »
Metalloenzymes, structural motifs, and inorganic models.
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Science 261, 701-708
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Physical Interaction of CcmC with Heme and the Heme Chaperone CcmE during Cytochrome c Maturation.
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Measurement of Intracellular Free Zinc Concentrations Accompanying Zinc-Induced Neuronal Death.
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