[PIN+]ing down the mechanism of prion appearance.
[PIN+]ing down the mechanism of prion appearance.
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[PIN ] 查明朊病毒出现的机制。
DOI：
10.1093/femsyr/foy026
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发表时间：
2018
影响因子：
3.2
通讯作者：
Serio,TriciaR
中科院分区：
文献类型：
--
作者：
Serio,TriciaR
Prion是一种构象灵活的蛋白质，能够采用一种天然状态和与蛋白质功能变化相关的一系列替代状态。这些替代状态很容易聚集成淀粉样蛋白聚集体，这为底层构象的自我复制和传递提供了一种结构，从而出现了新的表型。在体内，淀粉样蛋白的出现是一种罕见的事件，既受Pron蛋白聚集倾向的调节，也受其细胞环境的调节。这些力量通常是如何相交以抑制淀粉样蛋白的出现，以及这些限制如何绕过这些限制以创建仅限蛋白质的表型仍然知之甚少。研究最广泛，也可能是最易于实验的系统来探索调节淀粉样蛋白外观的机制是酿酒酵母的[PIN+]普里恩。对于天然酵母蛋白和在酵母中表达的人类蛋白来说，淀粉样蛋白的出现都需要[Pin+]。这些观察表明，[PIN+]有助于体内其他蛋白绕过淀粉样蛋白调节机制。Prion出现的几个模型与目前的观察结果相一致，突出了这个过程的复杂性，以及为了更好地了解这些事件的调节机制而必须解决的问题。
Prions are conformationally flexible proteins capable of adopting a native state and a spectrum of alternative states associated with a change in the function of the protein. These alternative states are prone to assemble into amyloid aggregates, which provide a structure for self-replication and transmission of the underlying conformer and thereby the emergence of a new phenotype. Amyloid appearance is a rare eventin vivo, regulated by both the aggregation propensity of prion proteins and their cellular environment. How these forces normally intersect to suppress amyloid appearance and the ways in which these restrictions can be bypassed to create protein-only phenotypes remain poorly understood. The most widely studied and perhaps most experimentally tractable system to explore the mechanisms regulating amyloid appearance is the [PIN+] prion ofSaccharomyces cerevisiae. [PIN+] is required for the appearance of the amyloid state for both native yeast proteins and for human proteins expressed in yeast. These observations suggest that [PIN+] facilitates the bypass of amyloid regulatory mechanisms by other proteinsin vivo. Several models of prion appearance are compatible with current observations, highlighting the complexity of the process and the questions that must be resolved to gain greater insight into the mechanisms regulating these events.