On the evolutionary significance and metal-binding characteristics of a monolobal transferrin from<i>Ciona intestinalis</i>

Tinoco, Arthur D.; Peterson, C. W.; Lucchese, Baldo; Doyle, Robert P.; Valentine, Ann M.

doi:10.1073/pnas.0705037105

Cited by 28 publications

(22 citation statements)

References 74 publications

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“…Proteins of cluster 2 are putative transferrins with no predicted conserved iron binding site (Table 1b); whereas, those transferrin genes diverging with human Tsf have predicted iron binding properties (Tables 1a-1b). We also included the transferrins of the tunicates that are invertebrates with a single lobe that binds iron (~40 kDa; CiTf1, HrTf1, HrTf2; [14,69,100,101]). In this analysis, they appear to have separated from the insect transferrins of clusters 1 and 2 (Fig.…”

Section: Sequencementioning

confidence: 99%

Insect transferrins: Multifunctional proteins

Geiser

Winzerling

2012

Biochimica et Biophysica Acta (BBA) - General Subjects

115

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Section: Sequencementioning

confidence: 99%

Insect transferrins: Multifunctional proteins

Geiser

Winzerling

2012

Biochimica et Biophysica Acta (BBA) - General Subjects

115

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“…Analogous proteins in C. intestinalis could be involved in the binding of iAs or its methylated metabolites. For example, nicatransferrin, a monolobal transferrin from C. intestinalis (Tinoco et al, 2008), could bind arsenicals in a manner analogous to As binding by mammalian transferrin (Zhang et al, 1998).…”

Section: Arsenic Biotransformation In Ciona Intestinalismentioning

confidence: 99%

Arsenic (+ 3 Oxidation State) Methyltransferase and the Methylation of Arsenicals in the Invertebrate Chordate Ciona intestinalis

Thomas

Nava

Cai

et al. 2009

Toxicological Sciences

103

118

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Biotransformation of inorganic arsenic (iAs) involves methylation catalyzed by arsenic (+ 3 oxidation state) methyltransferase (As3mt) yielding mono-, di-, and trimethylated arsenicals. To investigate the evolution of molecular mechanisms that mediate arsenic biotransformation, a comparative genomic approach focusing on the invertebrate chordate Ciona intestinalis was used. Bioinformatic analyses identified an As3mt gene in the C. intestinalis genome. Constitutive As3mt RNA expression was observed in heart, branchial sac, and gastrointestinal tract. Adult animals were exposed to 0 or 1 ppm of iAs for 1 or 5 days. Steady-state As3mt RNA expression in the gastrointestinal tract was not modulated significantly by 5 days of exposure to iAs. Tissue levels of iAs and its methylated metabolites were determined by hydride generation-cryotrapping-gas chromatography-atomic absorption spectrometry. At either time point, exposure to iAs significantly increased concentrations of iAs and its methylated metabolites in tissues. After 5 days of exposure, total speciated arsenic concentrations were highest in branchial sac (3705 ng/g), followed by heart (1019 ng/g) and gastrointestinal tract (835 ng/g). At this time point, the sum of the speciated arsenical concentrations in gastrointestinal tract and heart equaled or exceeded that of iAs; in branchial sac, iAs was the predominant species present. Ciona intestinalis metabolizes iAs to its methylated metabolites, which are retained in tissues. This metabolic pattern is consistent with the presence of an As3mt ortholog in its genome and constitutive expression of the gene in prominent organs, making this basal chordate a useful model to examine the evolution of arsenic detoxification.

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“…To appreciate the interplay between structure and function, we will briefly survey structural details of sTf and TfR that are important for Fe(III) cellular delivery and, potentially, the delivery of other metals. STf is a bilobal protein that is believed to be part of an evolutionary gene duplication event from monolobal transferrins, [13,14] which appears to have increased its Fe(III)-binding capacity and affinity [15]. It consists of 679 residues that are divided into the N-terminus lobe (N-lobe; residues 1-331) and the C-terminus lobe (C-lobe; residues 339-679) and they are held together by a linker peptide that contains residues 332-338 [16] (Figure 1 and 3).…”

Section: Structural Characterization Of Stf and Its Fe(iii) Bindingmentioning

confidence: 99%

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

Benjamín-Rivera¹,

Cardona-Rivera²,

Vázquez-Maldonado³

et al. 2020

Preprint

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Serum transferrin (sTf) plays a pivotal role in regulating iron biodistribution and homeostasis within the body. The molecular details of sTf Fe(III) binding, blood transport, and cellular delivery through transferrin receptor-mediated endocytosis are generally well-understood. Emerging interest exists in exploring sTf complexation of nonferric metals as it facilitates the therapeutic potential and toxicity of several of them. This review explores recent X-ray structural and physiologically relevant metal speciation studies to understand how sTf partakes in the bioactivity of key non-redox active hard Lewis acidic metals. It challenges preconceived notions of sTf structure function correlations that were based exclusively on the Fe(III) model by revealing distinct coordination modalities that nonferric metal ions can adopt and different modes of binding to metal-free and Fe(III)-bound sTf that can directly influence how they enter into cells and, ultimately, how they may impact human health. This knowledge informs on biomedical strategies to engineer sTf as a delivery vehicle for metal-based diagnostic and therapeutic agents in the cancer field. It is the intention of this work to open new avenues for characterizing the functionality and medical utility of nonferric-bound sTf and to expand the significance of this protein in the context of bioinorganic chemistry.

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On the evolutionary significance and metal-binding characteristics of a monolobal transferrin fromCiona intestinalis

Cited by 28 publications

References 74 publications

Insect transferrins: Multifunctional proteins

Insect transferrins: Multifunctional proteins

Arsenic (+ 3 Oxidation State) Methyltransferase and the Methylation of Arsenicals in the Invertebrate Chordate Ciona intestinalis

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

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