Symmetry disruption commits vault particles to disassembly.

Symmetry disruption commits vault particles to disassembly.
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对称性破坏使拱顶粒子解体。

DOI:
10.1126/sciadv.abj7795
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发表时间:
2022-02-11
期刊:
影响因子:
13.6
通讯作者:
Verdaguer N
Verdaguer N
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Guerra P;González-Alamos M;Llauró A;Casañas A;Querol-Audí J;de Pablo PJ;Verdaguer N

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穹窿是一种普遍存在的核糖核蛋白颗粒,参与多种细胞过程,作为递送多种货物的纳米器件具有很好的应用前景。穹窿壳由多个拷贝的主要穹窿蛋白的对称结合组装而成,最初产生半穹窿。两个半拱顶的成对反平行关联产生整个拱顶。在这里,使用的拱顶重组重建和结构技术的组合,我们的特点是拱顶打开过程的分子决定因素。这个过程开始于拱顶腰部的松弛,导致内腔的膨胀。然后,在穹窿中部的氨基末端结构域的局部脱离引发了导致孔的构象变化,从而促进进入承载货物的内腔。这些结果告知了迄今为止未表征的拱顶循环步骤,并将有助于当前利用拱顶进行定制货物交付的工程工作。Cryo-EM通过破坏D39对称性揭示了拱顶打开的机制。
Vaults are ubiquitous ribonucleoprotein particles involved in a diversity of cellular processes, with promising applications as nanodevices for delivery of multiple cargos. The vault shell is assembled by the symmetrical association of multiple copies of the major vault protein that, initially, generates half vaults. The pairwise, anti-parallel association of two half vaults produces whole vaults. Here, using a combination of vault recombinant reconstitution and structural techniques, we characterized the molecular determinants for the vault opening process. This process commences with a relaxation of the vault waist, causing the expansion of the inner cavity. Then, local disengagement of amino-terminal domains at the vault midsection seeds a conformational change that leads to the aperture, facilitating access to the inner cavity where cargo is hosted. These results inform a hitherto uncharacterized step of the vault cycle and will aid current engineering efforts leveraging vault for tailored cargo delivery. Cryo-EM reveals the mechanism of vault opening by disruption of D39 symmetry.
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