Prevalence and species distribution of the low-complexity, amyloid-like, reversible, kinked segment structural motif in amyloid-like fibrils.

Prevalence and species distribution of the low-complexity, amyloid-like, reversible, kinked segment structural motif in amyloid-like fibrils.
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DOI:
10.1016/j.jbc.2021.101194
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发表时间:
2021-10
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
Eisenberg DS
Eisenberg DS
中科院分区:
其他
文献类型:
--
作者:
Hughes MP;Goldschmidt L;Eisenberg DS

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无膜细胞器(MLO)是细胞中重要的动态反应中心,在没有膜的情况下将细胞质分隔开。蛋白质低复杂性结构域之间的多价相互作用有助于MLO组织。以前,我们使用计算方法来识别称为低复杂性淀粉样蛋白可逆扭结片段(LARKS)的结构基序,这些结构基序促进相变形成水凝胶,并且在参与MLO的人类蛋白质中很常见。在这里,我们寻找LARKS的蛋白质组中的六个模式生物:智人,黑腹果蝇,恶性疟原虫,酿酒酵母,结核分枝杆菌和大肠杆菌,以了解LARKS的分布在不同物种的蛋白质组。我们发现LARKS在结核分枝杆菌、黑腹果蝇和智人中大量存在,但在酿酒酵母和恶性疟原虫中不存在。LARKS具有高甘氨酸含量,这使得能够形成扭结,如已知的富含LARKS的TDP43、FUS和hnRNPA 2的淀粉样蛋白生成结构所例示的,这三种蛋白已知参与MLO。这些结果支持了LARKS作为一种进化结构基序的观点。基于这些结果,我们还建立了LARKSdb Web服务器,它允许用户在他们感兴趣的蛋白质序列中搜索LARKS。
Membraneless organelles (MLOs) are vital and dynamic reaction centers in cells that compartmentalize the cytoplasm in the absence of a membrane. Multivalent interactions between protein low-complexity domains contribute to MLO organization. Previously, we used computational methods to identify structural motifs termed low-complexity amyloid-like reversible kinked segments (LARKS) that promote phase transition to form hydrogels and that are common in human proteins that participate in MLOs. Here, we searched for LARKS in the proteomes of six model organisms: Homo sapiens, Drosophila melanogaster, Plasmodium falciparum, Saccharomyces cerevisiae, Mycobacterium tuberculosis, and Escherichia coli to gain an understanding of the distribution of LARKS in the proteomes of various species. We found that LARKS are abundant in M. tuberculosis, D. melanogaster, and H. sapiens but not in S. cerevisiae or P. falciparum. LARKS have high glycine content, which enables kinks to form as exemplified by the known LARKS-rich amyloidogenic structures of TDP43, FUS, and hnRNPA2, three proteins that are known to participate in MLOs. These results support the idea of LARKS as an evolved structural motif. Based on these results, we also established the LARKSdb Web server, which permits users to search for LARKS in their protein sequences of interest.
DOI: 10.1038/s41467-020-19512-3
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