当前位置: X-MOL 学术Sci. Adv. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Uncovering the universality of self-replication in protein aggregation and its link to disease
Science Advances ( IF 13.6 ) Pub Date : 2022-08-12 , DOI: 10.1126/sciadv.abn6831
Georg Meisl 1 , Catherine K Xu 1 , Jonathan D Taylor 2 , Thomas C T Michaels 1 , Aviad Levin 1 , Daniel Otzen 3 , David Klenerman 1, 4 , Steve Matthews 2 , Sara Linse 5 , Maria Andreasen 1, 6 , Tuomas P J Knowles 1, 7
Affiliation  

Fibrillar protein aggregates are a hallmark of a range of human disorders, from prion diseases to dementias, but are also encountered in several functional contexts. Yet, the fundamental links between protein assembly mechanisms and their functional or pathological roles have remained elusive. Here, we analyze the aggregation kinetics of a large set of proteins that self-assemble by a nucleated-growth mechanism, from those associated with disease, over those whose aggregates fulfill functional roles in biology, to those that aggregate only under artificial conditions. We find that, essentially, all such systems, regardless of their biological role, are capable of self-replication. However, for aggregates that have evolved to fulfill a structural role, the rate of self-replication is too low to be significant on the biologically relevant time scale. By contrast, all disease-related proteins are able to self-replicate quickly compared to the time scale of the associated disease. Our findings establish the ubiquity of self-replication and point to its potential importance across aggregation-related disorders.

中文翻译:

揭示蛋白质聚集中自我复制的普遍性及其与疾病的联系

纤维状蛋白聚集体是一系列人类疾病的标志,从朊病毒病到痴呆症,但也存在于几种功能环境中。然而,蛋白质组装机制与其功能或病理作用之间的基本联系仍然难以捉摸。在这里,我们分析了大量蛋白质的聚集动力学,这些蛋白质通过有核生长机制自组装,从与疾病相关的蛋白质,到聚集体在生物学中发挥功能作用的蛋白质,再到仅在人工条件下聚集的蛋白质。我们发现,基本上,所有这些系统,无论其生物学角色如何,都能够自我复制。然而,对于已经进化以发挥结构作用的聚合体,自我复制的速率太低,在生物学相关的时间尺度上不显着。相比之下,与相关疾病的时间尺度相比,所有与疾病相关的蛋白质都能够快速自我复制。我们的研究结果确立了自我复制的普遍性,并指出其在聚集相关疾病中的潜在重要性。
更新日期:2022-08-12
down
wechat
bug