A physical model describing the interaction of nuclear transport receptors with FG nucleoporin domain assemblies
Abstract
The permeability barrier of nuclear pore complexes (NPCs) controls bulk nucleocytoplasmic exchange. It consists of nucleoporin domains rich in phenylalanine-glycine motifs (FG domains). As a bottom-up nanoscale model for the permeability barrier, we have used planar films produced with three different end-grafted FG domains and quantitatively analyzed the binding of two different nuclear transport receptors (NTRs), NTF2 and Importin β, together with the concomitant film thickness changes. NTR binding caused only moderate changes in film thickness; the binding isotherms showed negative cooperativity and could all be mapped onto a single master curve. This universal NTR binding behavior - a key element for the transport selectivity of the NPC - was quantitatively reproduced by a physical model that treats FG domains as regular, flexible polymers, and NTRs as spherical colloids with a homogeneous surface, ignoring the detailed arrangement of interaction sites along FG domains and on the NTR surface.
Article and author information
Author details
Copyright
© 2016, Zahn et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,093
- views
-
- 730
- downloads
-
- 76
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Physics of Living Systems
- Computational and Systems Biology
Nuclear Pore Complexes (NPCs) are key cellular transporter that control nucleocytoplasmic transport in eukaryotic cells, but its transport mechanism is still not understood. The centerpiece of NPC transport is the assembly of intrinsically disordered polypeptides, known as FG nucleoporins, lining its passageway. Their conformations and collective dynamics during transport are difficult to assess in vivo. In vitro investigations provide partially conflicting results, lending support to different models of transport, which invoke various conformational transitions of the FG nucleoporins induced by the cargo-carrying transport proteins. We show that the spatial organization of FG nucleoporin assemblies with the transport proteins can be understood within a first principles biophysical model with a minimal number of key physical variables, such as the average protein interaction strengths and spatial densities. These results address some of the outstanding controversies and suggest how molecularly divergent NPCs in different species can perform essentially the same function.
-
- Physics of Living Systems
In social behavior research, the focus often remains on animal dyads, limiting the understanding of complex interactions. Recent trends favor naturalistic setups, offering unique insights into intricate social behaviors. Social behavior stems from chance, individual preferences, and group dynamics, necessitating high-resolution quantitative measurements and statistical modeling. This study leverages the Eco-HAB system, an automated experimental setup that employs radiofrequency identification tracking to observe naturally formed mouse cohorts in a controlled yet naturalistic setting, and uses statistical inference models to decipher rules governing the collective dynamics of groups of 10–15 individuals. Applying maximum entropy models on the coarse-grained co-localization patterns of mice unveils social rules in mouse hordes, quantifying sociability through pairwise interactions within groups, the impact of individual versus social preferences, and the effects of considering interaction structures among three animals instead of two. Reproducing co-localization patterns of individual mice reveals stability over time, with the statistics of the inferred interaction strength capturing social structure. By separating interactions from individual preferences, the study demonstrates that altering neuronal plasticity in the prelimbic cortex – the brain structure crucial for sociability – does not eliminate signatures of social interactions, but makes the transmission of social information between mice more challenging. The study demonstrates how the joint probability distribution of the mice positions can be used to quantify sociability.