A bimodal distribution of two distinct categories of intrinsically disordered structures with separate functions in FG nucleoporins

Justin Yamada, Joshua L. Phillips, Samir Patel, Gabriel Goldfien, Alison Calestagne-Morelli, Hans Huang, Ryan Reza, Justin Acheson, Viswanathan V Krishnan, Shawn Newsam, Ajay Gopinathan, Edmond Y Lau, Michael E. Colvin, Vladimir N. Uversky, Michael F. Rexacha

Research output: Contribution to journalArticle

193 Scopus citations

Abstract

Nuclear pore complexes (NPCs) gate the only conduits for nucleocytoplasmic transport in eukaryotes. Their gate is formed by nucleoporins containing large intrinsically disordered domains with multiple phenylalanine-glycine repeats (FG domains). In combination, these are hypothesized to form a structurally and chemically homogeneous network of random coils at the NPC center, which sorts macromolecules by size and hydrophobicity. Instead, we found that FG domains are structurally and chemically heterogeneous. They adopt distinct categories of intrinsically disordered structures in non-random distributions. Some adopt globular, collapsed coil configurations and are characterized by a low charge content. Others are highly charged and adopt more dynamic, extended coil conformations. Interestingly, several FG nucleoporins feature both types of structures in a bimodal distribution along their polypeptide chain. This distribution functionally correlates with the attractive or repulsive character of their interactions with collapsed coil FG domains displaying cohesion toward one another and extended coil FG domains displaying repulsion. Topologically, these bipartite FG domains may resemble sticky molten globules connected to the tip of relaxed or extended coils. Within the NPC, the crowding of FG nucleoporins and the segregation of their disordered structures based on their topology, dimensions, and cohesive character could force the FG domains to form a tubular gate structure or transporter at the NPC center featuring two separate zones of traffic with distinct physicochemical properties.

Original languageEnglish (US)
Pages (from-to)2205-2224
Number of pages20
JournalMolecular and Cellular Proteomics
Volume9
Issue number10
DOIs
StatePublished - Oct 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Analytical Chemistry

Fingerprint Dive into the research topics of 'A bimodal distribution of two distinct categories of intrinsically disordered structures with separate functions in FG nucleoporins'. Together they form a unique fingerprint.

  • Cite this

    Yamada, J., Phillips, J. L., Patel, S., Goldfien, G., Calestagne-Morelli, A., Huang, H., Reza, R., Acheson, J., Krishnan, V. V., Newsam, S., Gopinathan, A., Lau, E. Y., Colvin, M. E., Uversky, V. N., & Rexacha, M. F. (2010). A bimodal distribution of two distinct categories of intrinsically disordered structures with separate functions in FG nucleoporins. Molecular and Cellular Proteomics, 9(10), 2205-2224. https://doi.org/10.1074/mcp.M000035-MCP201