Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oviparously developing embryos of the crustacean Artemia franciscana encyst and enter diapause, exhibiting a level of stress tolerance seldom seen in metazoans. The extraordinary stress resistance of encysted Artemia embryos is thought to depend in part on the regulated synthesis of artemin, a ferritin superfamily member. The objective of this study was to better understand artemin function, and to this end the protein was synthesized in Escherichia coli and purified to apparent homogeneity. Purified artemin consisted of oligomers approximately 700 kDa in molecular mass that dissociated into monomers and a small number of dimers upon SDS/PAGE. Artemin inhibited heat-induced aggregation of citrate synthase in vitro, an activity characteristic of molecular chaperones and shown here to be shared by apoferritin and ferritin. This is the first report that apoferritin/ferritin may protect cells from stress other than by iron sequestration. Stably transfected mammalian cells synthesizing artemin were more resistant to heat and H(2)O(2) than were cells transfected with vector only, actions also shared by molecular chaperones such as the small heat shock proteins. The data indicate that artemin is a structurally modified ferritin arising either from a common ancestor gene or by duplication of the ferritin gene. Divergence, including acquisition of a C-terminal peptide extension and ferroxidase center modification, eliminated iron sequestration, but chaperone activity was retained. Therefore, because artemin accumulates abundantly during development, it has the potential to protect embryos from stress during encystment and diapause without adversely affecting iron metabolism.
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PMID:Functional characterization of artemin, a ferritin homolog synthesized in Artemia embryos during encystment and diapause. 1725 68

Diapause-destined embryos of the crustacean, Artemia franciscana, accumulate large amounts of an oligomeric, heat-stable, molecular chaperone termed artemin, a cysteine-enriched ferritin homologue. In this study, cysteines 22, 61, 166, and 172 of artemin were substituted with alanines, respectively yielding ArtC22A, ArtC61A, ArtC166A, and ArtC172A. Wild-type and modified artemins were synthesized in transformed bacteria and purified. As measured by heat-induced denaturation of citrate synthase in vitro, each substitution reduced chaperone activity, with ArtC172A the least active. Protein modeling indicated that C172 is close to a region of surface hydrophobicity, also present in ferritin, suggesting that this site contributes to chaperone activity. Only slight differences in oligomer molecular mass were apparent between artemin variants, but ArtC22A and ArtC61A displayed significantly reduced thermostability, perhaps due to the disruption of an inter-subunit disulphide bridge. In contrast, ArtC172A was thermostable, reflecting the location of C172 on the oligomer surface and that it contributes minimally to artemin stabilization. To our knowledge, this is the initial study of structure/function relationships within a ferritin homologue of importance in diapause and the first to indicate that a defined region of hydrophobicity contributes to artemin and ferritin chaperoning.
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PMID:The structural stability and chaperone activity of artemin, a ferritin homologue from diapause-destined Artemia embryos, depend on different cysteine residues. 2087 95