title: Facilitated aggregation of FG nucleoporins under molecular crowding conditions.
abstract: Intrinsically disordered and phenylalanine-glycine-rich nucleoporins (FG Nups) form a crowded and selective transport conduit inside the NPC that can only be transited with the help of nuclear transport receptors (NTRs). It has been shown in vitro that FG Nups can assemble into two distinct appearances, amyloids and hydrogels. If and how these phenomena are linked and if they have a physiological role still remains unclear. Using a variety of high-resolution fluorescence and electron microscopic (EM) tools, we reveal that crowding conditions mimicking the NPC environment can accelerate the aggregation and amyloid formation speed of yeast and human FG Nups by orders of magnitude. Aggregation can be inhibited by NTRs, providing a rationale on how the cell might control amyloid formation of FG Nups. The superb spatial resolving power of EM also reveals that hydrogels are enlaced amyloid fibres, and these findings have implications for existing transport models and for NPC assembly.
authors.affiliation: EMBL, Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Milles
authors.forename: Khanh
authors.initials: K
authors.lastname: Huy Bui
authors.forename: Christine
authors.initials: C
authors.lastname: Koehler
authors.forename: Mikhail
authors.initials: M
authors.lastname: Eltsov
authors.forename: Martin
authors.initials: M
authors.lastname: Beck
authors.forename: Edward A
authors.initials: EA
authors.lastname: Lemke
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D003911:Dextrans / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D007700:Kinetics; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000648:ultrastructure; D009994:Osmolar Concentration; D016062:Porosity; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D028961:beta Karyopherins / Q000737:chemistry
chemical_list: D000682:Amyloid; D003911:Dextrans; D020100:Hydrogels; C079377:NUP153 protein, human; D028861:Nuclear Pore Complex Proteins; D028961:beta Karyopherins