Self-assembly and regulation of protein cages from pre-organised coiled-coil modules.

Self-assembly and regulation of protein cages from pre-organised coiled-coil modules.
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DOI:
10.1038/s41467-021-21184-6
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发表时间:
2021-02-11
影响因子:
16.6
通讯作者:
Jerala R
Jerala R
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lapenta F;Aupič J;Vezzoli M;Strmšek Ž;Da Vela S;Svergun DI;Carazo JM;Melero R;Jerala R

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卷曲螺旋蛋白质折纸(CCPO)是一种用于多肽纳米结构从头设计的模块化策略。CCPO折叠由串联的正交卷曲螺旋(CC)二聚体形成肽的顺序定义,其中单链蛋白质被编程折叠成多面体笼。类似于DNA纳米技术,从几条链中自组装基于CC的纳米结构可以促进更复杂组件的设计和功能的引入。在这里,我们展示了一个从头三角形双金字塔折叠的设计,包括18个CC-形成段,并定义了从不对称和伪对称的预组织结构模块的双金字塔笼的双链自组装的策略。此外,通过引入一个蛋白酶切割位点和掩蔽的界面CC形成的两链双锥笼的片段,我们设计了一个蛋白水解介导的构象开关。这种策略可以扩展到其他模块蛋白质折叠,促进动态多链CC为基础的复合物的建设。卷曲螺旋蛋白质折纸是一种基于卷曲螺旋二聚体形成肽的多肽纳米结构的从头设计策略,其中单链蛋白质折叠成多面体笼。在这里,作者设计了一个单链三角双锥,并证明了双锥可以自组装为异二聚体复合物,包括预定义的亚基。
Coiled-coil protein origami (CCPO) is a modular strategy for the de novo design of polypeptide nanostructures. CCPO folds are defined by the sequential order of concatenated orthogonal coiled-coil (CC) dimer-forming peptides, where a single-chain protein is programmed to fold into a polyhedral cage. Self-assembly of CC-based nanostructures from several chains, similarly as in DNA nanotechnology, could facilitate the design of more complex assemblies and the introduction of functionalities. Here, we show the design of a de novo triangular bipyramid fold comprising 18 CC-forming segments and define the strategy for the two-chain self-assembly of the bipyramidal cage from asymmetric and pseudo-symmetric pre-organised structural modules. In addition, by introducing a protease cleavage site and masking the interfacial CC-forming segments in the two-chain bipyramidal cage, we devise a proteolysis-mediated conformational switch. This strategy could be extended to other modular protein folds, facilitating the construction of dynamic multi-chain CC-based complexes. Coiled-coil protein origami is a strategy for the de novo design of polypeptide nanostructures based on coiled-coil dimer forming peptides, where a single chain protein folds into a polyhedral cage. Here, the authors design a single-chain triangular bipyramid and also demonstrate that the bipyramid can be self-assembled as a heterodimeric complex, comprising pre-defined subunits.
DOI: 10.1007/978-1-62703-691-7_18
发表时间: 2014
期刊: Methods in molecular biology (Clifton, N.J.)
影响因子: --
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DOI: 10.1038/s41467-021-21185-5
发表时间: 2021-02-11
影响因子: 16.6
作者:
Aupič J;Strmšek Ž;Lapenta F;Pahovnik D;Pisanski T;Drobnak I;Ljubetič A;Jerala R
通讯作者: Jerala R
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发表时间: 2012-01-01
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发表时间: 2019-06-12
影响因子: 15
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