title: A bimodal distribution of two distinct categories of intrinsically disordered structures with separate functions in FG nucleoporins.
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.
authors.affiliation: Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, California 95064, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Yamada
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Phillips
authors.forename: Samir
authors.initials: S
authors.lastname: Patel
authors.forename: Gabriel
authors.initials: G
authors.lastname: Goldfien
authors.forename: Alison
authors.initials: A
authors.lastname: Calestagne-Morelli
authors.forename: Hans
authors.initials: H
authors.lastname: Huang
authors.forename: Ryan
authors.initials: R
authors.lastname: Reza
authors.forename: Justin
authors.initials: J
authors.lastname: Acheson
authors.forename: Viswanathan V
authors.initials: VV
authors.lastname: Krishnan
authors.forename: Shawn
authors.initials: S
authors.lastname: Newsam
authors.forename: Ajay
authors.initials: A
authors.lastname: Gopinathan
authors.forename: Edmond Y
authors.initials: EY
authors.lastname: Lau
authors.forename: Michael E
authors.initials: ME
authors.lastname: Colvin
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
authors.forename: Michael F
authors.initials: MF
authors.lastname: Rexach
mesh_terms: D000595:Amino Acid Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D005998:Glycine / Q000737:chemistry; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D028861:Nuclear Pore Complex Proteins; D010649:Phenylalanine; D005998:Glycine