Amyloids: from pathogenesis to function

Abstract

The term "amyloids" refers to fibrillar protein aggregates with cross-β structure. They have been a subject of intense scrutiny since the middle of the previous century. First, this interest is due to association of amyloids with dozens of incurable human diseases called amyloidoses, which affect hundreds of millions of people. However, during the last decade the paradigm of amyloids as pathogens has changed due to an increase in understanding of their role as a specific variant of quaternary protein structure essential for the living cell. Thus, functional amyloids are found in all domains of the living world, and they fulfill a variety of roles ranging from biofilm formation in bacteria to long-term memory regulation in higher eukaryotes. Prions, which are proteins capable of existing under the same conditions in two or more conformations at least one of which having infective properties, also typically have amyloid features. There are weighty reasons to believe that the currently known amyloids are only a minority of their real number. This review provides a retrospective analysis of stages in the development of amyloid biology that during the last decade resulted, on one hand, in reinterpretation of the biological role of amyloids, and on the other hand, in the development of systems biology of amyloids, or amyloidomics.

Amyloids and prions in plants: Facts and perspectives

“…QN-rich proteins represent approximately one-third of the currently known amyloids. 97 For other amyloid-forming proteins, strict patterns of the primary structure have not been identified. However, various amino acids have different amyloidogenic propensities.…”

Amyloid properties of the yeast cell wall protein Toh1 and its interaction with prion proteins Rnq1 and Sup35

“…Binding of amyloids with Congo red is accompanied with an applegreen birefringence in polarized light [5]. Along with pathological amyloids connected with different amyloidassociated disorders, there are functional amyloids that perform various vital functions and have been found in a broad range of living organisms [6][7][8][9]. Infectious amyloids, called prions, cause incurable neurodegenerative diseases in human and mammals [10] and heritable phenotypical traits in unicellular eucaryota [11,12].…”

The Pub1 and Upf1 Proteins Act in Concert to Protect Yeast from Toxicity of the [<em>PSI</em>⁺] Prion

“…Similar to other amyloids, most prions are formed in a process of highly ordered non-covalent polymerization of partially misfolded protein monomers. The ability to form amyloids is a common inherent feature of conformationally flexible proteins, which in many cases contain intrinsically disordered domains and, since such proteins are widespread in nature, amyloids are found in a wide range of organisms from mammals to bacteria, where they can have both deleterious and beneficial effects [1,2]. While in mammals prions cause neurodegenerative diseases, in fungi they mediate non-chromosomal inheritance of several phenotypic traits [3,4].…”