Department of Chemical and Systems Biology, Stanford University, 269 Campus Drive, Stanford, CA 94305, United States.
Department of Chemical and Systems Biology, Stanford University, 269 Campus Drive, Stanford, CA 94305, United States; Department of Developmental Biology, Stanford University, 269 Campus Drive, Stanford, CA 94305, United States.
J Mol Biol. 2018 Nov 2;430(23):4607-4618. doi: 10.1016/j.jmb.2018.07.017. Epub 2018 Jul 19.
A central tenet of molecular biology is that heritable information is stored in nucleic acids. However, this paradigm has been overturned by a group of proteins called "prions." Prion proteins, many of which are intrinsically disordered, can adopt multiple conformations, at least one of which has the capacity to self-template. This unusual folding landscape drives a form of extreme epigenetic inheritance that can be stable through both mitotic and meiotic cell divisions. Although the first prion discovered-mammalian PrP-is the causative agent of debilitating neuropathies, many additional prions have now been identified that are not obviously detrimental and can even be adaptive. Intrinsically disordered regions, which endow proteins with the bulk property of "phase-separation," can also be drivers of prion formation. Indeed, many protein domains that promote phase separation have been described as prion-like. In this review, we describe how prions lie at the crossroads of phase separation, epigenetic inheritance, and evolutionary adaptation.
分子生物学的一个基本原则是，可遗传的信息储存在核酸中。然而，这一范式被一类被称为“朊病毒”的蛋白质所颠覆。朊病毒蛋白，其中许多是固有无序的，能够采用多种构象，其中至少有一种具有自我模板的能力。这种不寻常的折叠景观驱动了一种极端的表观遗传遗传，这种遗传可以通过有丝分裂和减数分裂细胞分裂来稳定。尽管第一个被发现的朊病毒——哺乳动物 PrP——是导致衰弱性神经病变的原因，但现在已经发现了许多其他显然没有危害甚至可以适应的朊病毒。赋予蛋白质“相分离”总体特性的无序区域，也可能是朊病毒形成的驱动因素。事实上，许多促进相分离的蛋白质结构域都被描述为类朊病毒。在这篇综述中，我们描述了朊病毒如何处于相分离、表观遗传遗传和进化适应的十字路口。
