Plasticity of an Ultrafast Interaction Between Nucleoporins and Nuclear Transport Receptors

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2015 Oct 13

PMID 26456112

Citations 149

Authors

Sigrid Milles

Davide Mercadante

Iker Valle Aramburu

Malene Ringkjobing Jensen

Niccolo Banterle

Christine Koehler

Swati Tyagi

Jane Clarke

Sarah L Shammas

Martin Blackledge

Frauke Grater

Edward A Lemke

Affiliations

Soon will be listed here.

Abstract

The mechanisms by which intrinsically disordered proteins engage in rapid and highly selective binding is a subject of considerable interest and represents a central paradigm to nuclear pore complex (NPC) function, where nuclear transport receptors (NTRs) move through the NPC by binding disordered phenylalanine-glycine-rich nucleoporins (FG-Nups). Combining single-molecule fluorescence, molecular simulations, and nuclear magnetic resonance, we show that a rapidly fluctuating FG-Nup populates an ensemble of conformations that are prone to bind NTRs with near diffusion-limited on rates, as shown by stopped-flow kinetic measurements. This is achieved using multiple, minimalistic, low-affinity binding motifs that are in rapid exchange when engaging with the NTR, allowing the FG-Nup to maintain an unexpectedly high plasticity in its bound state. We propose that these exceptional physical characteristics enable a rapid and specific transport mechanism in the physiological context, a notion supported by single molecule in-cell assays on intact NPCs.

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