Spectrin, the major protein component of the erythrocyte membrane skeleton has chaperone like activity and is known to bind membrane phospholipids and hemoglobin. We have probed the chaperone activity of spectrin in presence of hemoglobin and phospholipid SUVs of different compositions to elucidate the effect of phospholipid/hemoglobin binding on chaperone function. It is seen that spectrin displays a preference for hemoglobin over other substrates leading to a decrease in chaperone activity in presence of hemoglobin. A competition is seen to exist between phospholipid binding and chaperone function of spectrin, in a dose dependent manner with the greatest extent of decrease being seen in case of phospholipid vesicles containing aminophospholipids e.g. PS and PE which may have implications in diseases like hereditary spherocytosis where mutation in spectrin is implicated in its detachment from cell membrane. To gain a clearer understanding of the chaperone like activity of spectrin under in-vivo like conditions we have investigated the effect of macromolecular crowders as well as phosphorylation and glycation states on chaperone activity. It is seen that the presence of non-specific, protein and non-protein macromolecular crowders do not appreciably affect chaperone function. Phosphorylation also does not affect the chaperone function unlike glycation which progressively diminishes chaperone activity. We propose a model where chaperone clients adsorb onto spectrin's surface and processes that bind to and occlude these surfaces decrease chaperone activity.

中文翻译：

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红细胞膜蛋白伴侣的潜力：血红蛋白相互作用，大分子拥挤，磷酸化和糖基化的影响。

血影蛋白是红细胞膜骨架的主要蛋白质成分，具有类似伴侣的活性，并且已知会结合膜磷脂和血红蛋白。我们已经研究了血红蛋白和不同组成的磷脂SUVs存在下血影蛋白的伴侣活性，以阐明磷脂/血红蛋白结合对伴侣功能的影响。可见血影蛋白对血红蛋白的显示优于其他底物，从而导致在存在血红蛋白的情况下伴侣活性降低。磷脂结合和血影蛋白的伴侣功能之间存在竞争，其剂量依赖性，在含有氨基磷脂的磷脂囊泡（例如）的情况下，最大程度的降低 PS和PE可能与遗传球菌病等疾病有关，其中血影蛋白的突变与其从细胞膜上脱落有关。为了更清楚地了解在体内条件下血影蛋白的伴侣蛋白样活性，我们研究了大分子拥挤剂以及磷酸化和糖基化状态对伴侣蛋白活性的影响。可以看出，非特异性，蛋白质和非蛋白质大分子拥挤剂的存在不会明显影响伴侣蛋白的功能。磷酸化也不会影响分子伴侣的功能，而糖基化会逐渐降低分子伴侣的活性。我们提出了一个模型，其中伴侣客户吸收到血影蛋白的表面上，而结合并阻塞这些表面的过程会降低伴侣活性。