Energetics of Transport through the Nuclear Pore Complex - PubMed (original) (raw)

Energetics of Transport through the Nuclear Pore Complex

Ali Ghavami et al. PLoS One. 2016.

Abstract

Molecular transport across the nuclear envelope in eukaryotic cells is solely controlled by the nuclear pore complex (NPC). The NPC provides two types of nucleocytoplasmic transport: passive diffusion of small molecules and active chaperon-mediated translocation of large molecules. It has been shown that the interaction between intrinsically disordered proteins that line the central channel of the NPC and the transporting cargoes is the determining factor, but the exact mechanism of transport is yet unknown. Here, we use coarse-grained molecular dynamics simulations to quantify the energy barrier that has to be overcome for molecules to pass through the NPC. We focus on two aspects of transport. First, the passive transport of model cargo molecules with different sizes is studied and the size selectivity feature of the NPC is investigated. Our results show that the transport probability of cargoes is significantly reduced when they are larger than ∼5 nm in diameter. Secondly, we show that incorporating hydrophobic binding spots on the surface of the cargo effectively decreases the energy barrier of the pore. Finally, a simple transport model is proposed which characterizes the energy barrier of the NPC as a function of diameter and hydrophobicity of the transporting particles.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1

Fig 1. The geometrical model of the NPC and cargoes.

(A) (left) The core scaffold of the NPC, reconstructed based on the structural model proposed in [45], (right) a snapshot taken from an umbrella sampling simulation for a cargo with D = 10 nm. (B) Geometrical representation of a model cargo smaller than 5.0 nm in diameter and (C), composite cargoes larger than 5.0 nm. (D) Geometrical representation of a model Kap-cargo complex with 7 binding spots. (E) The inert cargoes with different diameters and a Kap-cargo complex as used in the simulations.

Fig 2

Fig 2. Potential of mean force curves along the central axis of the NPC (r = 0) for cargoes with D = 10, 7.3, 6.0, 4.2 and 2.0 nm.

Fig 3

Fig 3. The energy barrier G versus diameter D of the cargoes.

The dashed line is a quadratic fit to the data and the error bars indicate the standard deviation of the data for the interval -5.0 nm < z < 5.0 nm and 20 nm < z <27 nm.

Fig 4

Fig 4. The 2D density plots of the FG-Nups taken from the umbrella simulations.

The vertical distance from the center of the cargo to the central plane of the NPC is (A) 30 nm, (B) 15.6 nm, (C) 8.3 and (D) 1.1 nm, respectively.

Fig 5

Fig 5. The potential of mean force along the radial direction of the NPC (at z = −2.5 nm) for a cargo with D = 10 nm.

Fig 6

Fig 6. The free energy curves along the central axis of the NPC (r = 0), for a Kap-cargo complex of diameter D = 10 nm with different spacings d between the binding spots on its surface.

The inset shows the energy barrier versus spacing d. The interaction energy between individual binding spots and the FG-repeats is −5.2 kJ.mol−1.

Fig 7

Fig 7. The free energy curves along the central axis of the NPC (r = 0), for a Kap-cargo complex of diameter D = 10 nm with different number of binding spots n.

The inset shows the energy barrier versus the number of binding spots d. The interaction energy between individual binding spots and the FG-repeats is −5.2 kJ.mol−1.

Fig 8

Fig 8. Contour plot of the energy barrier G of the NPC as a function of cargo diameter D and number of hydrophobic binding spots n.

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This research was funded by the Zernike Institute for Advanced Materials at the University of Groningen. The authors thank SURFsara (www.surfsara.nl) for the support in using the Lisa Compute Cluster. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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