The energy landscape of modular repeat proteins: Topology determines folding mechanism in the ankyrin family
The energy landscape of modular repeat proteins: Topology determines folding mechanism in the ankyrin family
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DOI：
10.1016/j.jmb.2005.09.078
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发表时间：
2005-12-02
影响因子：
5.6
通讯作者：
Wolynes, PG
中科院分区：
文献类型：
--
作者：
Ferreiro, DU;Cho, SS;Wolynes, PG
由重复氨基酸基序组成的蛋白质在所有生命王国中都很丰富，尤其是在高等真核生物中。含有重复序列的蛋白质自组织成细长的非球状结构。决定球状域折叠的相同一般基本原理是否也适用于这些扩展拓扑？使用捕获完美漏斗能量景观的基于简化结构的模型，我们调查了含有锚蛋白重复的蛋白质的预测折叠机制。锚蛋白家族是研究最广泛的非球状折叠类别之一。仅基于天然接触的模型再现了这些蛋白质折叠的大部分实验观察结果，包括让人想起成核传播生长的折叠机制。模拟和实验结果的结合表明，非球状蛋白质的折叠可以通过漏斗状能量景观准确地描述，其中拓扑结构在折叠机制中起着决定性作用。 (c) 2005 Elsevier Ltd. 保留所有权利。
Proteins consisting of repeating amino acid motifs are abundant in all kingdoms of life, especially in higher eukaryotes. Repeat-containing proteins self-organize into elongated non-globular structures. Do the same general underlying principles that dictate the folding of globular domains apply also to these extended topologies? Using a simplified structure-based model capturing a perfectly funneled energy landscape, we surveyed the predicted mechanism of folding for ankyrin repeat containing proteins. The ankyrin family is one of the most extensively studied classes of non-globular folds. The model based only on native contacts reproduces most of the experimental observations on the folding of these proteins, including a folding mechanism that is reminiscent of a nucleation propagation growth. The confluence of simulation and experimental results suggests that the folding of non-globular proteins is accurately described by a funneled energy landscape, in which topology plays a determinant role in the folding mechanism. (c) 2005 Elsevier Ltd. All rights reserved.