Forced folding of a disordered protein accesses an alternative folding landscape.
Forced folding of a disordered protein accesses an alternative folding landscape.
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DOI：
10.1002/cphc.201402661
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发表时间：
2015-01-12
期刊：
影响因子：
--
通讯作者：
Deniz AA
中科院分区：
文献类型：
--
作者：
Moosa MM;Ferreon AC;Deniz AA
胞内无序蛋白（IDP）参与多种细胞功能。许多IDP可以与多个结合伴侣相互作用，导致其折叠成替代配体特异性功能结构。对于这种多结构IDP，关键问题是这些多结构是否完全编码在蛋白质序列中，就像许多球状蛋白质一样。为了回答这个问题，我们采用了单分子和集成技术相结合的方法来比较配体诱导和渗透压剂强迫的α-突触核蛋白折叠。我们的研究结果揭示了蛋白质折叠景观的上下文依赖性调制，这表明蛋白质的天然折叠的代码部分编码在其一级序列中，并且仅在与结合伴侣相互作用后完成。我们的研究结果表明，细胞相互作用在扩大无序蛋白质的折叠和功能方面发挥着关键作用。
Intrinsically disordered proteins (IDPs) are involved in diverse cellular functions. Many IDPs can interact with multiple binding partners, resulting in their folding into alternative ligand-specific functional structures. For such multi-structural IDPs, a key question is whether these multiple structures are fully encoded in the protein sequence, as is the case in many globular proteins. To answer this question, here we employed a combination of single-molecule and ensemble techniques to compare ligand-induced and osmolyte-forced folding of α-synuclein. Our results reveal context-dependent modulation of the protein’s folding landscape, suggesting that the codes for the protein’s native folds are partially encoded in its primary sequence, and are completed only upon interaction with binding partners. Our findings suggest a critical role for cellular interactions in expanding the repertoire of folds and functions available to disordered proteins.
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