Limits...
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.

Show MeSH

Related in: MedlinePlus

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.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4764519&req=5

pone.0148876.g001: 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.

Mentions: A simplified geometrical model of the NPC is built based on the geometry of the core scaffold of the yeast NPC and the FG-Nups are anchored at the predicted positions inside the pore [45, 46]. The scaffold is modeled using hard-sphere beads with a diameter of 5.0 nm which are assumed to have no interaction with the FG-nups (see Fig 1A).


Energetics of Transport through the Nuclear Pore Complex.

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

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.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0148876.g001: 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.
Mentions: A simplified geometrical model of the NPC is built based on the geometry of the core scaffold of the yeast NPC and the FG-Nups are anchored at the predicted positions inside the pore [45, 46]. The scaffold is modeled using hard-sphere beads with a diameter of 5.0 nm which are assumed to have no interaction with the FG-nups (see Fig 1A).

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