Reference: Milles S, et al. (2015) Plasticity of an ultrafast interaction between nucleoporins and nuclear transport receptors. Cell 163(3):734-45

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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.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Milles S, Mercadante D, Aramburu IV, Jensen MR, Banterle N, Koehler C, Tyagi S, Clarke J, Shammas SL, Blackledge M, ... Show all
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