Interaction of erythroid spectrin with hemoglobin variants: implications in β-thalassemia

Datta, Poppy; Chakrabarty, Sudipa Basu; Chakrabarty, Amit; Chakrabarti, Abhijit

doi:10.1016/s1079-9796(03)00019-6

Cited by 26 publications

(28 citation statements)

References 30 publications

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“…The potentials of the dimeric spectrin and the two subunits to prevent aggregation of both insulin and ADH better than that of the tetrameric spectrin, actually present in the intact membrane skeleton indicate against the chaperone-like function of spec- trin inside the erythrocytes. However, under different pathophysiological conditions, when the spectrin-based skeletal integrity is altered, the chaperone activity of dimeric spectrin could be useful in interacting with non-native and denatured proteins (34).…”

Section: Discussionmentioning

confidence: 99%

“…Nonerythroid spectrin also localizes predominantly along cellular plasma membranes (21). Spectrin binds to a wide range of ligands like hemein and protoporphyrin (24), antitumor antibiotics of aureolic acid group, chromomycin, and mithramycin (25), the local anesthetic dibucaine (26), fluorescence probes like Prodan and pyrene (27,28), metal ions like calcium and molybdenum (29,30), other proteins like actin (31), globin chains and hemoglobin (32)(33)(34), calmodulin (35), and other skeletal proteins like ankyrin, adducin and Band 4.1 (21,36,37). Association of spectrin with other proteins are essential to establish the planar network along with additional interactions of fatty acids (38) and phospholipids (39 -41).…”

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confidence: 99%

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Chaperone Activity and Prodan Binding at the Self-associating Domain of Erythroid Spectrin

Bhattacharyya

Ray²,

Bhattacharya

et al. 2004

Journal of Biological Chemistry

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Spectrin, the major constituent protein of the erythrocyte membrane skeleton, exhibits chaperone activity by preventing the irreversible aggregation of insulin at 25°C and that of alcohol dehydrogenase at 50°C. The dimeric spectrin and the two subunits, ␣-spectrin and ␤-spectrin prevent such aggregation appreciably better, 70% in presence of dimeric spectrin at an insulin:spectrin ratio of 1:1, than that in presence of the tetramer of 25%. Our results also show that spectrin binds to denatured enzymes ␣-glucosidase and alkaline phosphatase during refolding and the reactivation yields are increased in the presence of the spectrin derivatives when compared with those refolded in their absence. The unique hydrophobic binding site on spectrin for the fluorescence probe, 6-propionyl-2-(dimethylamino)-naphthalene (Prodan) has been established to localize at the self-associating domain with the binding stoichiometry of one Prodan/both dimeric and tetrameric spectrin. The other fluorescence probe, 1-anilinonaphthalene-8-sulfonic acid, does not show such specificity for spectrin, and the binding stoichiometry is between 3 and 5 1-anilinonaphthalene-8-sulfonic acid/dimeric and tetrameric spectrin, respectively. Regions in ␣-and ␤-spectrins have been found to have sequence homology with known chaperone proteins. More than 50% similarities in ␣-spectrin near the N terminus with human Hsp90 and in ␤-spectrin near the C terminus with human Hsp90 and Escherichia coli DnaJ have been found, indicating a potential chaperone-like sequence to be present near the self-associating domain that is formed by portions of ␣-spectrin near the N terminus and the ␤-spectrin near the C terminus. There are other patches of sequences also in both the spectrin polypeptides, at the other termini as well as in the middle of the rod domain having significant homology with well known chaperone proteins.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Chaperone Activity and Prodan Binding at the Self-associating Domain of Erythroid Spectrin

Bhattacharyya

Ray²,

Bhattacharya

et al. 2004

Journal of Biological Chemistry

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“…The binding constant between spectrin and oxyHb is two orders of magnitude greater than that between spectrin and cdB3 [56]. The spectrin-Hb interaction is markedly stronger for HbA2 (the α 2 δ 2 Hb variant found in β-thalassemia patients).…”

Section: +mentioning

confidence: 93%

Erythrocyte Signal Transduction Pathways, their Oxygenation Dependence and Functional Significance

Barvitenko

Adragna

Weber³

2005

Cell Physiol Biochem

135

104

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Erythrocytes play a key role in human and vertebrate metabolism. Tissue O₂ supply is regulated by both hemoglobin (Hb)-O₂ affinity and erythrocyte rheology, a key determinant of tissue perfusion. Oxygenation-deoxygenation transitions of Hb may lead to re-organization of the cytoskeleton and signalling pathways activation/deactivation in an O₂-dependent manner. Deoxygenated Hb binds to the cytoplasmic domain of the anion exchanger band 3, which is anchored to the cytoskeleton, and is considered a major mechanism underlying the oxygenation-dependence of several erythrocyte functions. This work discusses the multiple modes of Hb-cytoskeleton interactions. In addition, it reviews the effects of Mg²⁺, 2,3-diphosphoglycerate, NO, shear stress and Ca²⁺, all factors accompanying the oxygenation-deoxygenation cycle in circulating red cells. Due to the extensive literature on the subject, the data discussed here, pertain mainly to human erythrocytes whose O₂ affinity is modulated by 2,3-diphosphoglycerate, ectothermic vertebrate erythrocytes that use ATP, and to bird erythrocytes that use inositol pentaphosphate.

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“…On the other hand, the role of the interaction of spectrin with various proteins in certain types of disease processes has started to emerge as an important factor in pathogenic conditions. For example, the affinity of binding of spectrin to hemoglobin and its variants has been shown to increase in b-thalassemic patients (Datta et al 2003). In summary, the implications of spectrin mediated interactions in cellular physiology in healthy and diseased states are beginning to be unraveled, and future research in this area appears promising.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…In order to establish the extensive two-dimensional intracellular network, spectrin interacts with a large number of proteins such as actin, ankyrin, adducin and band 4.1 (Hartwig 1994(Hartwig , 1995. Interestingly, the hemoglobin binding properties of spectrin have recently been established (Chakrabarti et al 2001;Datta et al 2003). The interaction of the spectrinbased protein network with the cytoplasmic surface of the membrane controls the elasticity of the bilayer membrane and erythrocyte shape.…”

Section: Introductionmentioning

confidence: 99%

Spectrin Organization and Dynamics: New Insights

2006

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Spectrin is the major constituent protein of the erythrocyte cytoskeleton which forms a filamentous network on the cytoplasmic face of the membrane by providing a scaffold for a variety of proteins. In this review, several aspects of spectrin organization are highlighted, particularly with respect to its ability to bind hydrophobic ligands and its interaction with membrane surfaces. The characteristic binding of the fluorescent hydrophobic probes Prodan and pyrene to spectrin, which allows an estimation of the polarity of the hydrophobic probe binding site, is illustrated. In addition, the contribution of uniquely localized and conserved tryptophan residues in the 'spectrin repeats' in these processes is discussed. A functional implication of the presence of hydrophobic binding sites in spectrin is its recently discovered chaperone-like activity. Interestingly, spectrin exhibits residual structural integrity even after denaturation which could be considered as a hallmark of cytoskeletal proteins. Future research could provide useful information about the possible role played by spectrin in cellular physiology in healthy and diseased states.

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Interaction of erythroid spectrin with hemoglobin variants: implications in β-thalassemia

Cited by 26 publications

References 30 publications

Chaperone Activity and Prodan Binding at the Self-associating Domain of Erythroid Spectrin

Chaperone Activity and Prodan Binding at the Self-associating Domain of Erythroid Spectrin

Erythrocyte Signal Transduction Pathways, their Oxygenation Dependence and Functional Significance

Spectrin Organization and Dynamics: New Insights

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