title: Prion formation by a yeast GLFG nucleoporin.
abstract: The self-assembly of proteins into higher order structures is both central to normal biology and a dominant force in disease. Certain glutamine/asparagine (Q/N)-rich proteins in the budding yeast Saccharomyces cerevisiae assemble into self-replicating amyloid-like protein polymers, or prions, that act as genetic elements in an entirely protein-based system of inheritance. The nuclear pore complex (NPC) contains multiple Q/N-rich proteins whose self-assembly has also been proposed to underlie structural and functional properties of the NPC. Here we show that an essential sequence feature of these proteins--repeating GLFG motifs--strongly promotes their self-assembly into amyloids with characteristics of prions. Furthermore, we demonstrate that Nup100 can form bona fide prions, thus establishing a previously undiscovered ability of yeast GLFG nucleoporins to adopt this conformational state in vivo.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA, USA. randal.halfmann@utsouthwestern.edu
authors.forename: Randal
authors.initials: R
authors.lastname: Halfmann
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Wright
authors.forename: Simon
authors.initials: S
authors.lastname: Alberti
authors.forename: Susan
authors.initials: S
authors.lastname: Lindquist
authors.forename: Michael
authors.initials: M
authors.lastname: Rexach
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D022022:Nuclear Pore / Q000737:chemistry / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000378:metabolism*; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000682:Amyloid; C077731:NUP100 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins