Prion Strains and Amyloid Polymorphism Influence Phenotypic Variation
نویسندگان
چکیده
The deposition of protein aggregates is a unifying feature of a large class of diseases known as protein conformational disorders, which includes Alzheimer disease and prion diseases. One of the most fascinating and puzzling aspects of such diseases is the phenomenon of amyloid polymorphism, whereby a single diseaseassociated protein forms different types of ordered aggregate structures. This is best exemplified in prion diseases, in which these different structures, called prion strains, are responsible for much of the variation in pathology and disease transmission. Here, we review the current knowledge of prion strains and amyloid polymorphism, highlighting how diversity in amyloid structure relates to phenotypic differences.
منابع مشابه
Extensive Diversity of Prion Strains Is Defined by Differential Chaperone Interactions and Distinct Amyloidogenic Regions
Amyloidogenic proteins associated with a variety of unrelated diseases are typically capable of forming several distinct self-templating conformers. In prion diseases, these different structures, called prion strains (or variants), confer dramatic variation in disease pathology and transmission. Aggregate stability has been found to be a key determinant of the diverse pathological consequences ...
متن کاملSpontaneous Variants of the [RNQ+] Prion in Yeast Demonstrate the Extensive Conformational Diversity Possible with Prion Proteins
Prion strains (or variants) are structurally distinct amyloid conformations arising from a single polypeptide sequence. The existence of prion strains has been well documented in mammalian prion diseases. In many cases, prion strains manifest as variation in disease progression and pathology, and in some cases, these prion strains also show distinct biochemical properties. Yet, the underlying b...
متن کاملCountering amyloid polymorphism and drug resistance with minimal drug cocktails.
Several fatal, progressive neurodegenerative diseases, including various prion and prion-like disorders, are connected with the misfolding of specific proteins. These proteins misfold into toxic oligomeric species and a spectrum of distinct self-templating amyloid structures, termed strains. Hence, small molecules that prevent or reverse these protein-misfolding events might have therapeutic ut...
متن کاملInfluence of prion variant and yeast strain variation on prion-molecular chaperone requirements.
Prions of budding yeast serve as a tractable model of amyloid behavior. Here we address the issue of the effect of yeast strain variation on prion stability, focusing also on the effect of amyloid conformation and the involvement of the co-chaperone Sis1, an essential J-protein partner of Hsp70. We found, despite an initial report to the contrary, that yeast strain background has little effect ...
متن کاملStrain-specific sequences required for yeast [PSI+] prion propagation.
Amyloid polymorphism underlies the prion strain phenomenon where a single protein polypeptide adopts different chain-folding patterns to form self-propagating cross-beta structures. Three strains of the yeast prion [PSI], namely [VH], [VK], and [VL], have been previously characterized and are amyloid conformers of the yeast translation termination factor Sup35. Here we define specific sequences...
متن کامل