Non-random-coil behavior as a consequence of extensive PPII structure in the denatured state.
Non-random-coil behavior as a consequence of extensive PPII structure in the denatured state.
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DOI：
10.1016/j.jmb.2008.07.005
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发表时间：
2008-09-26
影响因子：
5.6
通讯作者：
Haran, Gilad
中科院分区：
文献类型：
--
作者：
Cortajarena, Aitziber L.;Lois, Gregg;Sherman, Eilon;O'Hern, Corey S.;Regan, Lynne;Haran, Gilad
关键词：
未折叠的蛋白质可能含有天然或非天然的残余结构，这对折叠的热力学和动力学以及错误折叠和聚集疾病具有重要意义。然而，人们普遍认为，残余结构不应该影响变性链的全局尺寸标度，这服从无规卷曲聚合物的统计。在这里，我们使用单分子光学技术，荧光相关光谱，探测变性状态的一组重复蛋白质含有越来越多的相同的结构域，从2到20。这个集合的可用性使我们能够获得这些蛋白质的未折叠状态的标度律，这些蛋白质是异常紧凑的，强烈偏离随机卷曲统计。这种意想不到的行为的起源被追溯到广泛的非天然聚脯氨酸II螺旋结构的存在下，我们本地化的多肽链的特定片段。我们表明，实验观察到的影响PPII的变性状态的尺寸缩放可以很好地描述简单的聚合物模型。我们的研究结果表明，迄今未预见到的潜在的非天然结构，以诱导显着的压缩变性蛋白质，影响显着折叠途径和动力学。
Unfolded proteins may contain native or non-native residual structure, which has important implications for the thermodynamics and kinetics of folding as well as for misfolding and aggregation diseases. However, it has been universally accepted that residual structure should not affect the global size scaling of the denatured chain, which obeys the statistics of random coil polymers. Here we use a single-molecule optical technique, fluorescence correlation spectroscopy, to probe the denatured state of set of repeat proteins containing an increasing number of identical domains, from two to twenty. The availability of this set allows us to obtain the scaling law for the unfolded state of these proteins, which turns out to be unusually compact, strongly deviating from random-coil statistics. The origin of this unexpected behavior is traced to the presence of extensive non-native polyproline II helical structure, which we localize to specific segments of the polypeptide chain. We show that the experimentally observed effects of PPII on the size scaling of the denatured state can be well-described by simple polymer models. Our findings suggest an hitherto unforeseen potential of non-native structure to induce significant compaction of denatured proteins, affecting significantly folding pathways and kinetics.
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影响因子：
2.9
作者：
Gregor, I;Patra, D;Enderlein, J
通讯作者：
Enderlein, J
影响因子：
15
作者：
Kajander, T;Cortajarena, AL;Regan, L
通讯作者：
Regan, L
影响因子：
56.9
作者：
Klein-Seetharaman, J;Oikawa, M;Schwalbe, H
通讯作者：
Schwalbe, H
DOI：
10.1073/pnas.0510549103
发表时间：
2006-02-07
影响因子：
11.1
作者：
Makowska, J;Rodziewicz-Motowidlo, S;Scheraga, HA
通讯作者：
Scheraga, HA
影响因子：
64.8
作者：
Religa, TL;Markson, JS;Fersht, AR
通讯作者：
Fersht, AR