title: Control of amyloid assembly by autoregulation.
abstract: The assembly of proteins into amyloid fibrils can be an element of both protein aggregation diseases and a functional unit in healthy biological pathways. In both cases, it must be kept under tight control to prevent undesired aggregation. In normophysiology, proteins can self-chaperone amyloidogenic segments by restricting their conformational flexibility in an overall stabilizing protein fold. However, some aggregation-prone segments cannot be controlled in this manner and require additional regulatory elements to limit fibrillation. The present review summarizes different molecular mechanisms that proteins use to control their own assembly into fibrils, such as the inclusion of a chaperoning domain or a blocking segment in the proform, the controlled release of an amyloidogenic region from the folded protein, or the adjustment of fibrillation propensity according to pH. Autoregulatory elements can control disease-related as well as functional fibrillar protein assemblies and distinguish a group of self-regulating amyloids across a wide range of biological functions and organisms.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Landreh
authors.forename: Jan
authors.initials: J
authors.lastname: Johansson
authors.forename: Anna
authors.initials: A
authors.lastname: Rising
authors.forename: Jenny
authors.initials: J
authors.lastname: Presto
authors.forename: Hans
authors.initials: H
authors.lastname: Jörnvall
mesh_terms: D000682:Amyloid / Q000096:biosynthesis* / Q000737:chemistry; D000818:Animals; D005349:Fibroins / Q000096:biosynthesis; D005656:Fungal Proteins / Q000096:biosynthesis / Q000737:chemistry; D006706:Homeostasis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000737:chemistry; D008565:Membrane Proteins / Q000502:physiology; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D057165:Proteostasis Deficiencies / Q000209:etiology / Q000378:metabolism; D037721:Pulmonary Surfactant-Associated Protein C / Q000737:chemistry / Q000235:genetics; D058951:gp100 Melanoma Antigen / Q000096:biosynthesis
chemical_list: D000682:Amyloid; D005656:Fungal Proteins; C083891:HET-S protein, Podospora anserina; C499960:ITM2C protein, human; D007328:Insulin; D008565:Membrane Proteins; C548637:PMEL protein, human; D037721:Pulmonary Surfactant-Associated Protein C; D058951:gp100 Melanoma Antigen; D005349:Fibroins