Metastable network model of protein transport through nuclear pores - PubMed (original) (raw)

Metastable network model of protein transport through nuclear pores

T Kustanovich et al. Biophys J. 2004 Apr.

Abstract

To reconcile the observed selectivity and the high rate of translocation of cargo-importin complexes through nuclear pores, we propose that the core of the nuclear pore complex is blocked by a metastable network of phenylalanine and glycine nucleoporins. Although the network arrests the unfacilitated passage of objects larger than its mesh size, cargo-importin complexes act as catalysts that reduce the free energy barrier between the cross-linked and the dissociated states of the Nups, and open the network. Using Brownian dynamics simulations we calculate the distribution of passage times through the network for inert particles and cargo-importin complexes of different sizes and discuss the implications of our results for experiments on translocation of proteins through the nuclear pore complex.

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Figures

FIGURE 1

FIGURE 1

A snapshot of network fluctuations (a) and of the grafted chains (b) at T = 0.3. The beads shown are those with _c_-c (chain-chain) interaction.

FIGURE 2

FIGURE 2

The free energy of a chain versus the distance r of its free end from the wall. The combined contribution from the binding energy due to _c_-c interactions (dashed line) and from the elastic entropy (a parabolic curve) is given by solid line. Notice that the barrier height is much higher than the equilibrium binding free energy.

FIGURE 3

FIGURE 3

An IT (a) and CIC (b) with _R_t = 4 can pass through the network, the former due to thermal fluctuations (in a fully connected network ξ = 7.2) and the latter by also locally breaking the mesh.

FIGURE 4

FIGURE 4

CIC with _R_t = 8 passes through the network by breaking it.

FIGURE 5

FIGURE 5

Histogram of passage rates of IT with _R_t = 3 (▴), _R_t = 3.5 (•), and _R_t = 4 (▪). The passage rate is given in units of (1000 × t)−1.

FIGURE 6

FIGURE 6

Histogram of passage times of IT (•) and CIC with _N_t = 6 (▪), both of size _R_t = 4.

FIGURE 7

FIGURE 7

Histogram of passage times for IT with _R_t = 3 (▴), and for CICs with, _R_t = 4, _N_t = 6 (▪); and _R_t = 8, _N_t = 6 (•).

FIGURE 8

FIGURE 8

Histogram of passage times for IT with (a) _R_t = 4 (▪) and _R_t = 8 (•), and (b) _R_t = 12 through an open channel. Notice the difference of timescales in Fig. 8, a and b.

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