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Energetics of Transport through the Nuclear Pore Complex.

Ghavami A, van der Giessen E, Onck PR - PLoS ONE (2016)

Bottom Line: We focus on two aspects of transport.Our results show that the transport probability of cargoes is significantly reduced when they are larger than ∼5 nm in diameter.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.

View Article: PubMed Central - PubMed

Affiliation: Zernike Institute for Advanced Materials, University of Groningen, Groningen, the Netherlands.

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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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.
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pone.0148876.g007: 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.

Mentions: In order to quantify the effect of hydrophobicity of the Kap-cargo surface on active transport, PMF curves for Kap-cargo complexes are computed for a fixed spacing (d = 1.3 nm), but with varying number of binding spots (i.e., n = 3, 7 and 11), see Fig 7. The addition of 3 binding spots decreases the energy barrier from 10.5 kJ/mol (no binding spots, see Fig 2) to 7.3 kJ/mol. For n = 7, the energy barrier is on the order of kBT. Interestingly, by increasing the number of binding spots to n = 11, the barrier completely disappears and the NPC forms a potential well for the Kap-cargo complex. In this case the complex is attracted towards the pore and tends to stay in the central region of the NPC. Clearly, the probability for transport would be strongly reduced compared to a complex with 7 binding spots.


Energetics of Transport through the Nuclear Pore Complex.

Ghavami A, van der Giessen E, Onck PR - PLoS ONE (2016)

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.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4764519&req=5

pone.0148876.g007: 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.
Mentions: In order to quantify the effect of hydrophobicity of the Kap-cargo surface on active transport, PMF curves for Kap-cargo complexes are computed for a fixed spacing (d = 1.3 nm), but with varying number of binding spots (i.e., n = 3, 7 and 11), see Fig 7. The addition of 3 binding spots decreases the energy barrier from 10.5 kJ/mol (no binding spots, see Fig 2) to 7.3 kJ/mol. For n = 7, the energy barrier is on the order of kBT. Interestingly, by increasing the number of binding spots to n = 11, the barrier completely disappears and the NPC forms a potential well for the Kap-cargo complex. In this case the complex is attracted towards the pore and tends to stay in the central region of the NPC. Clearly, the probability for transport would be strongly reduced compared to a complex with 7 binding spots.

Bottom Line: We focus on two aspects of transport.Our results show that the transport probability of cargoes is significantly reduced when they are larger than ∼5 nm in diameter.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.

View Article: PubMed Central - PubMed

Affiliation: Zernike Institute for Advanced Materials, University of Groningen, Groningen, the Netherlands.

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.

Show MeSH
Related in: MedlinePlus