Nucleated conformational conversion and the replication of conformational information by a prion determinant.

By T. Serio, A. Cashikar, A. Kowal, G. Sawicki, J. Moslehi, Louise C. Serpell, M. Arnsdorf, Susan Lindquist. Science, 2000

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Prion proteins can serve as genetic elements by adopting distinct physical and functional states that are self-perpetuating and heritable. The critical region of one prion protein, Sup35, is initially unstructured in solution and then forms self-seeded amyloid fibers. We examined in vitro the mechanism by which this state is attained and replicated. Structurally fluid oligomeric complexes appear to be crucial intermediates in de novo amyloid nucleus formation. Rapid assembly ensues when these complexes conformationally convert upon association with nuclei. This model for replicating protein-based genetic information, nucleated conformational conversion, may be applicable to other protein assembly processes.

Subfields: Molecular Biology, Neurology, Nutrition and Dietetics

View Paper: https://www.semanticscholar.org/paper/9344a802061cd57794b13cab3fa8732f3c9c3f04

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Citations in the corpus

The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease (2012, background): “Yeast prion domains can switch between an intrinsically unfolded conformation (non-prion form) and an infectious cRoss-β conformation (prion form) (Alberti et al., 2009; Brachmann et al., 2005; Patel and Liebman, 2007; Serio et al., 2000; Sondheimer and Lindquist, 2000; Tanaka et al., 2004; Taylor e”
Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging. (2008, background): “Sup35 can exist as a soluble translation elongation factor or in a fibrillar state that allows translational readthrough and transmission as a “gain-of-function” prion state (Serio et al. 2000; True and Lindquist 2000).”
Protein aggregation kinetics, mechanism, and curve-fitting: a review of the literature. (2009, methodology): “The formation of larger aggregates occurs by nuclei of P acting as templates, which combine with and convert nuclei of C [28].”
Phase separation of a yeast prion protein promotes cellular fitness (2018, background): “The N-terminal region of Sup35 is intrinsically disordered and can be divided into two parts: an N-terminal prion domain (N) and a charged middle domain (M) (20, 21) (Fig.”
Solution conditions determine the relative importance of nucleation and growth processes in α-synuclein aggregation (2014, background): “It has been proposed that amyloid fibrils of different proteins, including α-synuclein (23, 24), can grow most efficiently by the addition of oligomers to the fibril ends.”
A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation. (2015, positive): “These states are also reminiscent of previously reported states that precede the formation of amyloid in in vitro aggregation reactions of the yeast prion Sup35 (Serio et al., 2000).”
What is the role of protein aggregation in neurodegeneration? (2005, background): “Alternative models for fibril formation are crisply articulated in two studies of the in vitro assembly of the yeast prion Sup35 NM aggregation domain, which conclude that fibril growth is mediated by the addition of either oligomer”
Functional amyloid--from bacteria to humans. (2007, background): “Soluble, oligomeric amyloid assemblies [ 67 ] are currently thought to be more toxic than insoluble amyloid fibers [8] .I n particular, pore-like amyloid oligomers that compromise membrane integrity have been observed and implicated in toxicity [8] .M a amyloid oligomers, if formed, could rupture th”
A systematic survey identifies prions and illuminates sequence features of prionogenic proteins (2009, background): “This composition promotes a disordered 4 molten-globule-like conformational ensemble, within which amyloid-nucleating contacts can be made (Serio et al., 2000; Wang et al., 2006; Mukhopadhyay et al., 2007).”
Direct Observation of the Interconversion of Normal and Toxic Forms of α-Synuclein (2012, methodology): “The simplest model that is consistent with these observations is a nucleation and growth model with a conformational conversion step, analogous to that used to describe the conformational conversion mechanism suggested for prions (Serio et al., 2000).”