title: The molecular mechanism of nuclear transport revealed by atomic-scale measurements.
abstract: Nuclear pore complexes (NPCs) form a selective filter that allows the rapid passage of transport factors (TFs) and their cargoes across the nuclear envelope, while blocking the passage of other macromolecules. Intrinsically disordered proteins (IDPs) containing phenylalanyl-glycyl (FG)-rich repeats line the pore and interact with TFs. However, the reason that transport can be both fast and specific remains undetermined, through lack of atomic-scale information on the behavior of FGs and their interaction with TFs. We used nuclear magnetic resonance spectroscopy to address these issues. We show that FG repeats are highly dynamic IDPs, stabilized by the cellular environment. Fast transport of TFs is supported because the rapid motion of FG motifs allows them to exchange on and off TFs extremely quickly through transient interactions. Because TFs uniquely carry multiple pockets for FG repeats, only they can form the many frequent interactions needed for specific passage between FG repeats to cross the NPC.
authors.affiliation: The Rockefeller University, New York, United States.
authors.forename: Loren E
authors.identifier: http://orcid.org/0000-0002-1104-0126
authors.initials: LE
authors.lastname: Hough
authors.affiliation: New York Structural Biology Center, New York, United States.
authors.forename: Kaushik
authors.identifier: http://orcid.org/0000-0002-9653-3842
authors.initials: K
authors.lastname: Dutta
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, United States.
authors.forename: Samuel
authors.initials: S
authors.lastname: Sparks
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, United States.
authors.forename: Deniz B
authors.initials: DB
authors.lastname: Temel
authors.affiliation: The Rockefeller University, New York, United States.
authors.forename: Alia
authors.initials: A
authors.lastname: Kamal
authors.affiliation: The Rockefeller University, New York, United States.
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Tetenbaum-Novatt
authors.affiliation: The Rockefeller University, New York, United States.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Rout
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, United States.
authors.forename: David
authors.identifier: http://orcid.org/0000-0001-6770-7172
authors.initials: D
authors.lastname: Cowburn
mesh_terms: D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000737:chemistry; D028884:Karyopherins / Q000378:metabolism* / Q000648:ultrastructure*; D009682:Magnetic Resonance Spectroscopy; D022022:Nuclear Pore / Q000378:metabolism* / Q000648:ultrastructure*
chemical_list: D028884:Karyopherins
keywords: S. cerevisiae; biophysics; cell biology; nuclear magnetic resonance; nuclear pore; nucleoporins; structural biology; transport factors