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 beta-N-acetylglucosamine-modified FG-Nups. Our results have implications for differential roles of distinctly spatially distributed FG-Nup.NTR interactions in the cell.

Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors / Tan Piau, Siong; Aramburu Iker, Valle; Mercadante, D; Tyagi, Swati; Chowdhury, Aritra; Spitz, Daniel; Shammas Sarah, L.; Graeter, Frauke; Lemke Edward, A.. - In: CELL REPORTS. - ISSN 2211-1247. - 22:13(2018), pp. 3660-3671. [10.1016/j.celrep.2018.03.022]

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

Mercadante D;
2018

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 beta-N-acetylglucosamine-modified FG-Nups. Our results have implications for differential roles of distinctly spatially distributed FG-Nup.NTR interactions in the cell.
2018
Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors / Tan Piau, Siong; Aramburu Iker, Valle; Mercadante, D; Tyagi, Swati; Chowdhury, Aritra; Spitz, Daniel; Shammas Sarah, L.; Graeter, Frauke; Lemke Edward, A.. - In: CELL REPORTS. - ISSN 2211-1247. - 22:13(2018), pp. 3660-3671. [10.1016/j.celrep.2018.03.022]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/950946
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