Designed folding pathway of modular coiled-coil-based proteins.
Designed folding pathway of modular coiled-coil-based proteins.
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DOI：
10.1038/s41467-021-21185-5
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发表时间：
2021-02-11
影响因子：
16.6
通讯作者：
Jerala R
中科院分区：
文献类型：
--
作者：
Aupič J;Strmšek Ž;Lapenta F;Pahovnik D;Pisanski T;Drobnak I;Ljubetič A;Jerala R
天然蛋白质的特征在于对于每个折叠唯一定义的复杂折叠途径。设计的卷曲螺旋蛋白折纸（CCPO）笼不同于天然的紧凑蛋白质，因为它们的折叠是由单个多肽链内正交成对相互作用的卷曲螺旋（CC）模块之间的离散长程相互作用规定的。在这里，我们证明了CCPO蛋白折叠在一个逐步顺序的途径。分子动力学模拟和停流Förster共振能量转移（FRET）的测量结果表明，CCPO的折叠主要是由CC模块的主要序列和随后的折叠中间体之间的有效链内距离，允许相同的CC模块被用于多个笼的边缘，从而放宽CCPO笼的设计要求。构造CCPO四面体所需的正交模块的数量可以从六个减少到三个不同的CC模块。折叠途径的逐步模块化性质提供了对串联重复蛋白质折叠的深入了解，并且可以用于基于给定的一组正交模块设计模块化蛋白质结构。卷曲螺旋蛋白质折纸（CCPO）是一种基于卷曲螺旋（CC）二聚体形成肽设计多面体笼状蛋白质折叠的策略。在这里，作者表明，CCPO蛋白折叠在一个多步骤的过程中，由CC模块之间的空间距离在初级序列和随后的折叠中间体，这使得使用相同的CC模块的CCPO四面体设计。
Natural proteins are characterised by a complex folding pathway defined uniquely for each fold. Designed coiled-coil protein origami (CCPO) cages are distinct from natural compact proteins, since their fold is prescribed by discrete long-range interactions between orthogonal pairwise-interacting coiled-coil (CC) modules within a single polypeptide chain. Here, we demonstrate that CCPO proteins fold in a stepwise sequential pathway. Molecular dynamics simulations and stopped-flow Förster resonance energy transfer (FRET) measurements reveal that CCPO folding is dominated by the effective intra-chain distance between CC modules in the primary sequence and subsequent folding intermediates, allowing identical CC modules to be employed for multiple cage edges and thus relaxing CCPO cage design requirements. The number of orthogonal modules required for constructing a CCPO tetrahedron can be reduced from six to as little as three different CC modules. The stepwise modular nature of the folding pathway offers insights into the folding of tandem repeat proteins and can be exploited for the design of modular protein structures based on a given set of orthogonal modules. Coiled-coil protein origami (CCPO) is a strategy for the design of polyhedral cage-shaped protein folds based on coiled-coil (CC) dimer-forming peptides. Here, the authors show that CCPO proteins fold in a multistep process governed by the spatial distance between CC modules in the primary sequence and subsequent folding intermediates, which enables the use of identical CC modules for the CCPO tetrahedron design.
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DOI：
10.1073/pnas.0812564106
发表时间：
2009-07-07
影响因子：
11.1
作者：
Jha, Santosh Kumar;Dhar, Deepak;Udgaonkar, Jayant B.
通讯作者：
Udgaonkar, Jayant B.
DOI：
10.1107/s2059798317005745
发表时间：
2017-05-01
影响因子：
2.2
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通讯作者：
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DOI：
10.1016/j.nima.2012.06.008
发表时间：
2012-10-11
影响因子：
1.4
作者：
Franke, Daniel;Kikhney, Alexey G.;Svergun, Dmitri I.
通讯作者：
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影响因子：
6.1
作者：
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影响因子：
2.9
作者：
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通讯作者：
CHAU, KH