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Amyloids are protein aggregates with the cross-β structure. The interest in amyloids is explained, on the one hand, by their role in the development of socially significant human neurodegenerative diseases, and on the other hand, by the discovery of functional amyloids, whose formation is an integral part of cellular processes. To date, more than a hundred proteins with the amyloid or amyloid-like properties have been identified. Studying the structure of amyloid aggregates has revealed a wide variety of protein conformations. In the review, we discuss the diversity of protein folds in the amyloid-like aggregates and the characteristic features of amyloid aggregates that determine their unusual properties, including stability and interaction with amyloid-specific dyes. The review also describes the diversity of amyloid aggregates and its significance for living organisms. [ABSTRACT FROM AUTHOR]

Over the recent decades, genome-wide association studies (GWAS) have dramatically changed the understanding of human genetics. A recent genetic data release by UK Biobank (UKB) has allowed many researchers worldwide to have comprehensive look into the genetic architecture of thousands of human phenotypes. In this study, we used GWAS summary statistics derived from the UKB cohort to investigate functional mechanisms of pleiotropic effects across the human phenome. We find that highly pleiotropic variants often correspond to broadly expressed genes with ubiquitous functions, such as matrisome components and cell growth regulators; and tend to colocalize with tissue-shared eQTLs. At the same time, signaling pathway components are more prevalent among highly pleiotropic genes compared to regulatory proteins such as transcription factors. Our results suggest that protein-level pleiotropy mediated by ubiquitously expressed genes is the most prevalent mechanism of pleiotropic genetic effects across the human phenome. [ABSTRACT FROM AUTHOR]

Endogenous yeast amyloids that control heritable traits and are frequently used as models for human amyloid diseases are termed yeast prions. Yeast prions, including the best studied ones ([PSI+] and [URE3]), propagate via intimate interactions with molecular chaperones. Different yeast prions exhibit differential responses to changes in levels, functionality or localization of the components of chaperone machinery. Here, we provide additional data confirming differential effects of chaperones (and specifically, Hsp40s) on yeast prions and summarize current knowledge of the mechanisms underlying chaperone specificities. Contrary to frequent statements in literature, overproduction of the Hsp104 chaperone antagonizes both [PSI+] and [URE3] prions, while overproduction of the Hsp70-Ssa1 chaperone antagonizes [URE3] prion only in some, but not in all strains. Recently, we demonstrated that the relocalization of a fraction of the Hsp40 chaperone Sis1 from the cytosol to the nucleus by the chaperone-sorting factor Cur1 exhibits opposite effects on [PSI+] and [URE3] prions. We suggest that the response of prions to changes in Sis1 localization represents a combination of the effects of Sis1 shortage on fragmentation of prion aggregates and on malpartition of prion aggregates during a cell division. Differences in sensitivity of prion fragmentation to Sis1 and in relative inputs of fragmentation and malpartition in prion propagation result in opposite effects of Sis1 relocalization on [PSI+] and [URE3]. [ABSTRACT FROM AUTHOR]