Spectrin interactome under normal and HbE-disease conditions

Bose, Deepak; Islam, Sk Ramiz; Saha, Sutapa; Chakrabarti, Abhijit

doi:10.1007/s42485-020-00050-x

Cited by 3 publications

(1 citation statement)

References 23 publications

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“…Spectrin is a cytoskeletal protein ubiquitous in metazoan (multicellular mitochondrial) cells 1,2 that acts as a liaison between the plasma membrane and the cellular interior, 3 on account of its interaction with a wide range of cytoplasmic, membrane-bound, and cytoskeletal proteins. 4 The emergence of this protein is believed to be linked to the evolution of metazoans from unicellular protists. 5 The spectrin meshwork (along with other cytoskeletal components such as actin) 6 imparts mechanical stability to the plasma membrane and regulates cellular morphology.…”

Section: ■ Introductionmentioning

confidence: 99%

Comparative Analysis of Tryptophan Dynamics in Spectrin and Its Constituent Domains: Insights from Fluorescence

et al. 2021

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Spectrin is a cytoskeletal protein ubiquitous in metazoan cells that acts as a liaison between the plasma membrane and the cellular interior and imparts mechanical stability to the plasma membrane. Spectrin is known to be highly dynamic, with an appreciable degree of torsional and segmental mobility. In this context, we have earlier utilized the red edge excitation shift (REES) approach to report the retention of restricted solvation dynamics and local structure in the vicinity of spectrin tryptophans on urea denaturation and loss of spectrin secondary structure. As a natural progression of our earlier work, in this work, we carried out a biophysical dissection of tryptophan solvation and rotational dynamics in spectrin and its constituent domains, in order to trace the origin of local structure retention observed in denatured spectrin. Our results show that the ankyrin binding domain (and, to a lesser extent, the β-tetramerization domain) is capable of retention of local structure, similar to that observed for intact spectrin. However, all α-chain domains studied exhibit negligible retention of local structure on urea denaturation. Such a stark chain-specific retention of local structure could originate from the fact that the β-chain domains possess specialized functions, where conservation of local (structural) integrity may be a prerequisite for optimum cellular function. To the best of our knowledge, these observations represent one of the first systematic biophysical dissections of spectrin dynamics in terms of its constituent domains and add to emerging literature on comprehensive domain-based analysis of spectrin organization, dynamics, and function.

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Section: ■ Introductionmentioning

confidence: 99%

Comparative Analysis of Tryptophan Dynamics in Spectrin and Its Constituent Domains: Insights from Fluorescence

et al. 2021

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Erythroid spectrin binding modulates peroxidase and catalase activity of heme proteins

et al. 2022

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Hemoglobin oxidation due to oxidative stress and disease conditions leads to the generation of ROS (reactive oxygen species) and membrane attachment of hemoglobin in-vivo, where its redox activity leads to peroxidative damage of membrane lipids and proteins. Spectrin, the major component of the red blood cell (RBC) membrane skeleton, is known to interact with hemoglobin and, here this interaction is shown to increase hemoglobin peroxidase activity in the presence of reducing substrate ABTS (2 0 , 2 0 -Azino-Bis-3-Ethylbenzothiazoline-6-Sulfonic Acid). It is also shown that in the absence of reducing substrate, spectrin forms covalently cross-linked aggregates with hemoglobin which display no peroxidase activity. This may have implications in the clearance of ROS and limiting peroxidative damage. Spectrin is found to modulate the peroxidase activity of different hemoglobin variants like A, E, and S, and of isolated globin chains from each of these variants. This may be of importance in disease states like sickle cell disease and HbE-β-thalassemia, where increased oxidative damage and free globin subunits are present due to the defects inherent in the hemoglobin variants associated with these diseases. This hypothesis is corroborated by lipid peroxidation experiments. The modulatory role of spectrin is shown to extend to other heme proteins, namely catalase and cytochrome-c. Experiments with free heme and Raman spectroscopy of heme proteins in the presence of spectrin show that structural alterations occur in the heme moiety of the heme proteins on spectrin binding, which may be the structural basis of increased enzyme activity.

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Erythroid spectrin binding modulates peroxidase and catalase activity of heme proteins

Bose

Aggarwal

Das

et al. 2021

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Hemoglobin oxidation due to oxidative stress and disease conditions leads to generation of ROS (reactive oxygen species) and membrane attachment of hemoglobin in-vivo, where its redox activity leads to peroxidative damage of membrane lipids and proteins. Spectrin, the major component of the RBC membrane skeleton, is known to interact with hemoglobin and, here this interaction is shown to increase hemoglobin peroxidase activity in the presence of reducing substrate ABTS (2, 2-Azino-Bis-3-Ethylbenzothiazoline-6-Sulfonic Acid). It is also shown that in the absence of reducing substrate, spectrin forms covalently cross-linked aggregates with hemoglobin which display no peroxidase activity. This may have implications in the clearance of ROS and limiting peroxidative damage. Spectrin is found to modulate the peroxidase activity of different hemoglobin variants like A, E, and S, and of isolated globin chains from each of these variants. This may be of importance in disease states like sickle cell disease and HbE-β-thalassemia, where increased oxidative damage and free globin subunits are present due to the defects inherent in the hemoglobin variants associated with these diseases. This hypothesis is corroborated by lipid peroxidation experiments. The modulatory role of spectrin is shown to extend to other heme proteins, namely catalase and cytochrome-c. Experiments with free heme and Raman spectroscopy of heme proteins in the presence of spectrin show that structural alterations occur in the heme moiety of the heme proteins on spectrin binding, which may be the structural basis of increased enzyme activity.

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Spectrin interactome under normal and HbE-disease conditions

Cited by 3 publications

References 23 publications

Comparative Analysis of Tryptophan Dynamics in Spectrin and Its Constituent Domains: Insights from Fluorescence

Comparative Analysis of Tryptophan Dynamics in Spectrin and Its Constituent Domains: Insights from Fluorescence

Erythroid spectrin binding modulates peroxidase and catalase activity of heme proteins

Erythroid spectrin binding modulates peroxidase and catalase activity of heme proteins

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