4,4′-Dianilino-1,1′-binaphtliyl-5,5′-sulfonate, a novel molecule having chaperone-like activity
4,4′-Dianilino-1,1′-binaphtliyl-5,5′-sulfonate, a novel molecule having chaperone-like activity
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DOI：
10.1016/j.bbrc.2005.01.164
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发表时间：
2005-04-15
影响因子：
3.1
通讯作者：
Chang, ZY
中科院分区：
文献类型：
--
作者：
Fu, XM;Zhang, XF;Chang, ZY
4，4 '-二苯胺基-1，1'-联萘基-5，5 '-磺酸盐（bis-ANS）和1-苯胺基萘-8-磺酸盐（ANS）是疏水探针，它们利用其结合部分未折叠蛋白质的疏水区域的能力，进而导致荧光增加，被广泛用于蛋白质折叠研究。在这里，我们揭示了一种新的伴侣样活性的双ANS，它作为一个非常有效的抑制剂的热或化学诱导的聚集的醇脱氢酶，胰岛素或大肠杆菌的全细胞提取物，与ANS显示出弱得多的效果。阐明这种活性的机制的研究表明，bis-ANS能够与变性蛋白形成稳定的可溶性聚集体，并在与易聚集蛋白孵育后显著增加其荧光强度。此外，我们发现bis-ANS能够防止柠檬酸合酶的热失活。这些观察结果表明，bis-ANS能够阻断暴露的疏水表面以抑制蛋白质聚集，其作用方式类似于小的热休克蛋白（分子伴侣的一个子类）。这里提供的数据，连同bis-ANS能够抑制朊病毒肽的淀粉样蛋白形成的报道[J. Biol. Chem. 279（2004）5346]，表明该分子除了其当前作为疏水探针的应用之外，还可以用作潜在的蛋白质稳定剂。(c)2005年由Elsevier Inc.出版
4,4'-Dianilino-1,1'-binapthyl-5,5'-sulfonate (bis-ANS) and 1-anilinonaphthalene-8-sulfonate (ANS) are hydrophobic probes that are widely used in protein folding studies, using their capacity to bind to hydrophobic regions of partially unfolded proteins and in turn leading to an increase in fluorescence. Here we reveal a novel chaperone-like activity for bis-ANS, which acted as a highly effective inhibitor for the thermal- or chemical-induced aggregation of alcohol dehydrogenase, insulin or the whole cell extract of Escherichia coli, with ANS showing a much weaker effect. The studies to elucidate the mechanism underlying this activity show that bis-ANS is able to form stable soluble aggregates with the denaturing proteins and dramatically increase its fluorescence intensity,upon incubation with aggregation-prone proteins. Moreover, we found that bis-ANS is able to prevent the heat inactivation of citrate synthase. These observations suggest that bis-ANS is able to block the exposed hydrophobic surfaces to suppress protein aggregation, acting in a way similar to what small heat shock proteins (one sub-class of molecular chaperones) do. The data presented here, together with the report that bis-ANS was able to suppress the amyloid formation of the prion peptide [J. Biol. Chem. 279 (2004) 5346], suggest that this molecule may be used as a potential protein stabilizer in addition to its current application as a hydrophobic probe. (c) 2005 Published by Elsevier Inc.