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多聚谷氨酰胺重复序列的结构可塑性。

The structural plasticity of polyglutamine repeats.

机构信息

IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135, Porto, Portugal; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135, Porto, Portugal.

IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135, Porto, Portugal; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135, Porto, Portugal.

出版信息

Curr Opin Struct Biol. 2023 Jun;80:102607. doi: 10.1016/j.sbi.2023.102607. Epub 2023 May 12.

DOI:10.1016/j.sbi.2023.102607
PMID:37178477
Abstract

From yeast to humans, polyglutamine (polyQ) repeat tracts are found frequently in the proteome and are particularly prominent in the activation domains of transcription factors. PolyQ is a polymorphic motif that modulates functional protein-protein interactions and aberrant self-assembly. Expansion of the polyQ repeated sequences beyond critical physiological repeat length thresholds triggers self-assembly and is linked to severe pathological implications. This review provides an overview of the current knowledge on the structures of polyQ tracts in the soluble and aggregated states and discusses the influence of neighboring regions on polyQ secondary structure, aggregation, and fibril morphologies. The influence of the genetic context of the polyQ-encoding trinucleotides is briefly discussed as a challenge for future endeavors in this field.

摘要

从酵母到人,多聚谷氨酰胺(polyQ)重复序列在蛋白质组中经常被发现,并且在转录因子的激活结构域中尤为突出。polyQ 是一种多态性基序,调节功能性蛋白-蛋白相互作用和异常的自组装。polyQ 重复序列的扩展超过临界生理重复长度阈值会触发自组装,并与严重的病理影响有关。本文综述了可溶性和聚集态 polyQ 序列的结构的最新知识,并讨论了邻近区域对 polyQ 二级结构、聚集和纤维形态的影响。简要讨论了 polyQ 编码三核苷酸的遗传背景的影响,这是该领域未来研究的一个挑战。

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