The Journal of Membrane Biology ( IF 2.3 ) Pub Date : 2020-09-29 , DOI: 10.1007/s00232-020-00142-1 Dipayan Bose 1, 2 , Abhijit Chakrabarti 1, 2
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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
中文翻译：
Spectrin 的多重功能：收敛效应
摘要
Spectrin 是一种多功能、多域蛋白质，在成熟人类红细胞的膜骨架中最为人所知。在这里，我们回顾了关于 Spectrin 的伴侣活动与其其他功能的串扰的文献。我们假设分子伴侣活性源自存在于单个“血影蛋白重复”域中的表面暴露的疏水斑块，并显示出膜磷脂结合功能与血影蛋白的分子伴侣活性之间的竞争。此外，我们表明翻译后修饰（例如糖基化）会屏蔽这些表面暴露的疏水性斑块，从而降低分子伴侣的功能。另一方面，与疏水性增加相关的低聚被视为增加疏水性。我们注意到 Spectrin 似乎更喜欢血红蛋白作为它的伴侣客户，与其他变性蛋白质优先结合。Spectrin 还已知与不稳定的血红蛋白变体相互作用，其亲和力高于正常血红蛋白的情况。我们提出血影蛋白的分子伴侣活性在血红蛋白的细胞生物化学中可能很重要，特别是在疾病的背景下。
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