ArticleThe Journal of biological chemistry2014
Oxidation-induced structural changes of ceruloplasmin foster NGR motif deamidation that promotes integrin binding and signaling.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 36 citations in OpenAlex.
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- Kinetic, thermodynamic, and ab initio insights of AsnGly isomerisation as a ticking time bomb for protein integrity.Communications chemistry · 2024Article
- Ceruloplasmin Deamidation in Neurodegeneration: From Loss to Gain of Function.International journal of molecular sciences · 2021Review
- Angiotensin II, Hypercholesterolemia, and Vascular Smooth Muscle Cells: A Perfect Trio for Vascular Pathology.International journal of molecular sciences · 2020Review
- Active compounds of herbs ameliorate impaired cognition in APP/PS1 mouse model of Alzheimer's disease.Aging · 2019Article
- Target Elimination-Denatured and Unstable Proteins, Environmental Toxins, Metabolic Wastes, Immunosuppressive Factors and Chronic Inflammatory Factors of Medical System for Chronic Diseases Prevention and Health Promotion: A Narrative Review.Iranian journal of public health · 2019Review
- Implications of Metal Binding and Asparagine Deamidation for Amyloid Formation.International journal of molecular sciences · 2018Review
- Ceruloplasmin replacement therapy ameliorates neurological symptoms in a preclinical model of aceruloplasminemia.EMBO molecular medicine · 2018Article
- Increased serotransferrin and ceruloplasmin turnover in diet-controlled patients with type 2 diabetes.Free radical biology & medicine · 2017Article
- Monocyte adhesion to atherosclerotic matrix proteins is enhanced by Asn-Gly-Arg deamidation.Scientific reports · 2017Article
- Ceruloplasmin functional changes in Parkinson's disease-cerebrospinal fluid.Molecular neurodegeneration · 2015Article
- Ceruloplasmin potentiates nitric oxide synthase activity and cytokine secretion in activated microglia.Journal of neuroinflammation · 2014Article
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10 authors at 3 institutions in 3 countries.
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Abstract
Asparagine deamidation occurs spontaneously in proteins during aging; deamidation of Asn-Gly-Arg (NGR) sites can lead to the formation of isoAsp-Gly-Arg (isoDGR), a motif that can recognize the RGD-binding site of integrins. Ceruloplasmin (Cp), a ferroxidase present in the cerebrospinal fluid (CSF), contains two NGR sites in its sequence: one exposed on the protein surface ((568)NGR) and the other buried in the tertiary structure ((962)NGR). Considering that Cp can undergo oxidative modifications in the CSF of neurodegenerative diseases, we investigated the effect of oxidation on the deamidation of both NGR motifs and, consequently, on the acquisition of integrin binding properties. We observed that the exposed (568)NGR site can deamidate under conditions mimicking accelerated Asn aging. In contrast, the hidden (962)NGR site can deamidate exclusively when aging occurs under oxidative conditions, suggesting that oxidation-induced structural changes foster deamidation at this site. NGR deamidation in Cp was associated with gain of integrin-binding function, intracellular signaling, and cell pro-adhesive activity. Finally, Cp aging in the CSF from Alzheimer disease patients, but not in control CSF, causes Cp deamidation with gain of integrin-binding function, suggesting that this transition might also occur in pathological conditions. In conclusion, both Cp NGR sites can deamidate during aging under oxidative conditions, likely as a consequence of oxidative-induced structural changes, thereby promoting a gain of function in integrin binding, signaling, and cell adhesion.
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