Prion formation by a yeast GLFG nucleoporin

Prion. Sep-Oct 2012;6(4):391-9. doi: 10.4161/pri.20199. Epub 2012 May 7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Amyloid / chemistry
  • Amyloid / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Pore / chemistry
  • Nuclear Pore / metabolism*
  • Nuclear Pore Complex Proteins / chemistry
  • Nuclear Pore Complex Proteins / metabolism*
  • Prions / chemistry
  • Prions / metabolism*
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Amyloid
  • NUP100 protein, S cerevisiae
  • Nuclear Pore Complex Proteins
  • Prions
  • Saccharomyces cerevisiae Proteins