Artificial Intracellular Filaments
Artificial Intracellular Filaments
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DOI：
10.1016/j.xcrp.2020.100085
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发表时间：
2020-07-22
影响因子：
8.9
通讯作者：
Xu, Bing
中科院分区：
文献类型：
--
作者：
Feng, Zhaoqianqi;Wang, Huaimin;Xu, Bing
细胞内蛋白丝普遍存在于细胞功能中，但在活细胞中形成真正的仿生小分子细胞内蛋白丝仍然是难以捉摸的。在这里，我们报道了通过磷酸化和三甲基化的异手性四肽的酶促形态转变，在原位形成一个小肽的自限性细胞内细丝。酶解去磷酸化减少了分子间的斥力静电相互作用，并将肽纳米颗粒转化为细丝，这些细丝表现出不同类型的交叉β结构，具有C7或C2对称，亲水性c端残基位于螺旋的外围。大分子拥挤促进肽丝形成束，从质膜延伸到核清膜，几乎不与内源性成分相互作用，包括细胞骨架。多肽的立体化学和翻译后修饰（PTM）是产生胞内束的关键。这项工作可能提供一种方法来获得失去的功能或提供理解正常和异常细胞内细丝的分子见解。
Intracellular protein filaments are ubiquitous for cellular functions, but forming bona fide biomimetic intracellular filaments of small molecules in living cells remains elusive. Here, we report the in situ formation of self-limiting intracellular filaments of a small peptide via enzymatic morphological transition of a phosphorylated and trimethylated heterochiral tetrapeptide. Enzymatic dephosphorylation reduces repulsive intermolecular electrostatic interactions and converts the peptidic nanoparticles into filaments, which exhibit distinct types of cross-beta structures with either C7 or C2 symmetries, with the hydrophilic C-terminal residues at the periphery of the helix. Macromolecular crowding promotes the peptide filaments to form bundles, which extend from the plasma membrane to nu-clear membrane and hardly interact with endogenous components, including cytoskeletons. Stereochemistry and post-translational modification (PTM) of peptides are critical for generating the intracellular bundles. This work may offer a way to gain lost functions or to provide molecular insights for understanding normal and aberrant intracellular filaments.