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Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors.

ABSTRACT: Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC). Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs. Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism when interacting with the export receptor CRM1. Association and dissociation rate constants are more than an order of magnitude lower than in the archetypal-fuzzy complex between FG-Nup153 and NTRs. Unexpectedly, this behavior appears not to be encoded selectively into CRM1 but rather into the FG-Nup214 sequence. The same distinct binding mechanisms are unperturbed in O-linked ?-N-acetylglucosamine-modified FG-Nups. Our results have implications for differential roles of distinctly spatially distributed FG-Nup?NTR interactions in the cell.

SUBMITTER: Tan PS 

PROVIDER: S-EPMC5898484 | biostudies-other | 2018 Mar

REPOSITORIES: biostudies-other

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Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors.

Tan Piau Siong PS   Aramburu Iker Valle IV   Mercadante Davide D   Tyagi Swati S   Chowdhury Aritra A   Spitz Daniel D   Shammas Sarah L SL   Gräter Frauke F   Lemke Edward A EA  

Cell reports 20180301 13

Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC). Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs. Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nu  ...[more]