Metal and Redox Modulation of Cysteine Protein Function

Giles, Niroshini M.; Watts, A; Giles, Gregory I.; Fry, Fiona H.; Littlechild, Jennifer A.; Jacob, Claus

doi:10.1016/s1074-5521(03)00174-1

Cited by 445 publications

(344 citation statements)

References 155 publications

Supporting

Mentioning

339

Contrasting

Unclassified

Order By: Relevance

“…Pca1p(250 -350) contains seven Cys residues that are frequently identified at metal binding sites in other proteins (61). Metal-sensing transcription regulators such as Mac1p and Ace1p in yeast and MTF-1 in higher eukaryotes, including mammals, also rely on Cys residues that likely bind with metal ions as a sensing mechanism (62).…”

Section: Discussionmentioning

confidence: 99%

Cadmium and Secondary Structure-dependent Function of a Degron in the Pca1p Cadmium Exporter

Smith

Wei

Zhao

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Protein turnover is a critical cellular process regulating biochemical pathways and destroying terminally misfolded or damaged proteins. Pca1p, a cadmium exporter in the yeast Saccharomyces cerevisiae, is rapidly degraded by the endoplasmic reticulum-associated degradation (ERAD) system via a cis-acting degron that exists at the 250 -350 amino acid region of Pca1p and is transferable to other proteins to serve as a degradation signal. Cadmium stabilizes Pca1p in a manner dependent on the degron. This suggested that cadmium-mediated masking of the degron impedes its interaction with the molecular factors involved in the ERAD. The characteristics and mechanisms of action of the degron in Pca1p and most of those in other proteins however remain to be determined. The results presented here indicate that specific cysteine residues in a degron of Pca1p sense cadmium. An unbiased approach selecting non-functional degrons indicated a critical role of hydrophobic amino acids in the degron for its function. A secondary structure modeling predicted the formation of an amphipathic helix. Site-directed mutagenesis confirmed the functional significance of the hydrophobic patch. Last, hydrophobic amino acids in the degron-and cadmium-binding region affected the interaction of Pca1p with the Ssa1p molecular chaperone, which is involved in ERAD. These results reveal the mechanism of action of the degron, which might be useful for the identification and characterization of other degrons.

show abstract

Section: Discussionmentioning

confidence: 99%

Cadmium and Secondary Structure-dependent Function of a Degron in the Pca1p Cadmium Exporter

Smith

Wei

Zhao

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Loss of protein sulfhydryls is often associated with reversible thiolation of proteins. Protein thiolation is apparently induced by different mechanisms that involve thiol/disulfide exchange or one or two electron oxidations of cysteinyl residues (Costa et al, 2003;Giles et al, 2003). Protein thiolation is potentially reversible by disulfide/thiol exchange or via the mediation of glutaredoxin and thioredoxin.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism by which ROS alter overall cellular redox state is thought to initially involve oxidation of free and protein-bound accessible thiols (Reed, 1986;Schafer and Buettner, 2001;Giles et al, 2003). Although there are several redox couples, which collectively establish the cellular redox state, reduced:oxidized glutathione (GSH:GSSG) is the most abundant pair.…”

Section: Introductionmentioning

confidence: 99%

Comparison of thiol redox state of mitochondria and homogenates of various tissues between two strains of mice with different longevities

Rebrin

Sohal

2004

Experimental Gerontology

View full text Add to dashboard Cite

The main purpose of this study was to determine if differences in life spans of two different strains of mice are associated with the thiol redox state of their tissues and mitochondria. A comparison, based on amounts of reduced and oxidized glutathione (GSH, GSSG) and reactive protein thiols, was made between short-lived SAM (P8) mice and the longer-lived C57BL/6 mice at 13 months of age. The average life span of the latter mouse strain is approximately 48% longer than the former strain. Analyses of plasma, tissue homogenates and mitochondria of liver, kidney, heart, brain and skeletal muscle indicated that, in general, amounts of GSH and reactive protein sulfhydryls and GSH:GSSG ratios were lower and concentrations of GSSG were higher in the SAM than the C57BL/6 mice. Differences in the redox state between the two strains were more consistent and pronounced in skeletal muscle than in other tissues, and in mitochondria than in their respective tissue homogenates. Overall, the results support the view that the shorter-lived SAM mice exhibit a relatively higher level of oxidative stress than the longer-lived C57BL/6 mice, which is consistent with the predictions of the oxidative stress hypothesis of aging. Intra-species comparisons may be useful for the identification of biochemical characteristics associated with the variations in life spans.

show abstract

“…1 These oxidations lead to the formation of intra-molecular and inter-molecular disulfide bridges (RS ÀI S ÀI R: cystine) or sulfenic, sulfinic and sulfonic acid, RS 0 OH, RS II O 2 H and RS IV O 3 H, respectively. Their interactions with transition metal ions are of biological importance 2 and can produce toxicity or lethality. Cysteines are, for instance, present in copper binding sites for copper homeostasis, which is known to be involved in two human disorders of copper transport, i.e.…”

Section: Introductionmentioning

confidence: 99%

The role of copper in cysteine oxidation: study of intra- and inter-molecular reactions in mass spectrometry

Prudent

Girault

2009

Metallomics

View full text Add to dashboard Cite

Cysteine-containing peptide oxidation was studied both by using an inert platinum electrode and a sacrificial electrode (copper or zinc) generating metallic ions in electrospray ionization mass spectrometry (ESI-MS). Using peptides containing one, two and three cysteines, we have compared the different chemical and electrochemical oxidation pathways of cysteine (RS ÀII H) to cystine (RS ÀI S ÀI R) and to sulfenic, sulfinic and sulfonic acid (RS 0 OH, RS II O 2 H and RS IV O 3 H, respectively). In the absence of copper ions, intra-molecular reactions were the most abundant, whereas inter-molecular reactions were found to be enhanced by the presence of copper ions. These cations favor the formation of 2 : 1 (peptide : copper) complexes compared to 1 : 1 complexes, thus enhancing the formation of inter-molecular bridges. This study highlights the importance of the position of cysteine inside a peptide during disulfide bridge formation.

show abstract

Metal and Redox Modulation of Cysteine Protein Function

Cited by 445 publications

References 155 publications

Cadmium and Secondary Structure-dependent Function of a Degron in the Pca1p Cadmium Exporter

Cadmium and Secondary Structure-dependent Function of a Degron in the Pca1p Cadmium Exporter

Comparison of thiol redox state of mitochondria and homogenates of various tissues between two strains of mice with different longevities

The role of copper in cysteine oxidation: study of intra- and inter-molecular reactions in mass spectrometry

Contact Info

Product

Resources

About