Multiple Functions of Spectrin: Convergent Effects
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Multiple Functions of Spectrin: Convergent Effects Dipayan Bose1,2 · Abhijit Chakrabarti1,2 Received: 9 July 2020 / Accepted: 19 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Spectrin is a multifunctional, multi-domain protein most well known in the membrane skeleton of mature human erythrocytes. Here we review the literature on the crosstalk of the chaperone activity of spectrin with its other functionalities. We hypothesize that the chaperone activity is derived from the surface exposed hydrophobic patches present in individual “spectrin-repeat” domains and show a competition between the membrane phospholipid binding functionality and chaperone activity of spectrin. Moreover, we show that post-translational modifications such as glycation which shield these surface exposed hydrophobic patches, reduce the chaperone function. On the other hand, oligomerization which is linked to increase of hydrophobicity is seen to increase it. We note that spectrin seems to prefer haemoglobin as its chaperone client, binding with it preferentially over other denatured proteins. Spectrin is also known to interact with unstable haemoglobin variants with a higher affinity than in the case of normal haemoglobin. We propose that chaperone activity of spectrin could be important in the cellular biochemistry of haemoglobin, particularly in the context of diseases. Graphic Abstract
Keywords Spectrin · Chaperone · Haemoglobin · ANS Abbreviations PRODAN 1-[6-(Dimethylamino)-2-naphthalenyl]-1propanone ANS 8-Anilino-1-naphthalene sulfonate * Abhijit Chakrabarti [email protected]; [email protected] 1
Crystallography & Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India
Homi Bhabha National Institute, Mumbai 400094, India
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Introduction Spectrin is a cytoskeletal protein which is found in the membrane skeleton of all metazoan cells examined till now. It is a hetero-dimer composed of α and β subunits with molecular masses of 280kDa and 246kDa, respectively. It is most well characterized in mammalian erythrocytes and neuronal cells. Spectrin is a multi-domain protein and is composed mostly of tandemly repeated homologous α-helical motifs called the “spectrin repeat” domains (Goodman et al. 1988).
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In mature human red blood cells (RBCs), the cell membrane is stabilized by a network of spectrin oligomers crosslinked with short actin filaments which are bound to the membrane and make the membrane skeleton (Chakrabarti et al. 2006). Erythrocyte spectrin is encoded by two genes, SPTA1 (UniProt P02549) for α-I spectrin and SPTB (UniProt P11277) for β-I spectrin. Spectrin is present in-vivo as a tetramer, which is formed by the “head-to-head” association of two hetero-dimers (Yoshino and Marchesi 1984). Both spectrin subunits consist mostly of tandem repeats of “spectrin repeat domains”, each of which is approximately 106 residues long, with about 30% identity between themselves, and they are alig
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