Managing Free-energy Barriers in Nuclear Pore Transport

Nielsen, Bjarne; Jeppesen, Claus; Ipsen, John Hjort

doi:10.1007/s10867-006-9029-5

Cited by 10 publications

(10 citation statements)

References 27 publications

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“…In agreement with the cohesive properties observed between GLFGdomains (Patel, S. S. et al, 2007), Kustanovich and Rabin predicted that FG-repeat domains would exhibit low equilibrium affinities for each other (Kustanovich, T., and Rabin, Y., 2004). In support of brush-like behavior for FG-domains (Lim, R. Y. et al, 2006), Nielsen et al showed that the conformational entropy of non-interacting FG-repeat domains was enough to provide for a robust barrier around the NPC by modelling the FG-repeat domains as surface grafted, polymeric random coils (Nielsen, B. et al, 2006). By solving a rigorous mathematical model of transport through the NPC, Zilman et al showed that selectivity, efficiency, directionality, and robustness of nucleocytoplasmic transport could be explained by combining the interaction strengths of binding to the flexible FG-repeat domains with the physics of diffusion inside a channel (Zilman, A. et al, 2007).…”

Section: In Silico Studies Of the Fg-domains And Barrier Functionmentioning

confidence: 96%

Biology and Biophysics of the Nuclear Pore Complex and Its Components

Lim

Ullman

Fahrenkrog

2008

International Review of Cell and Molecular Biology

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Nucleocytoplasmic exchange of proteins and ribonucleoprotein particles occurs via nuclear pore complexes (NPCs) that reside in the double membrane of the nuclear envelope (NE). Significant progress has been made the past few years in obtaining better structural resolution of the 3-D architecture of the NPC with the help of cryo-electron tomography and atomic structures of domains from nuclear pore proteins (nucleoporins). Biophysical and imaging approaches have helped elucidate how nucleoporins act as a selective barrier in nucleocytoplasmic transport. Nucleoporins act not only in trafficking of macromolecules but also in proper microtubule attachment to kinetochores, in the regulation of gene expression and signaling events associated with, for example, innate and adaptive immunity, development and neurodegenerative disorders. Recent research has also been focused on the dynamic processes of NPC assembly and disassembly that occur with each cell cycle. Here we review emerging results aimed at understanding the molecular arrangement of the NPC and how it is achieved, defining the roles of individual nucleoporins both at the NPC and at other sites within the cell, and finally deciphering how the NPC serves as both a barrier and a conduit of active transport.

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Section: In Silico Studies Of the Fg-domains And Barrier Functionmentioning

confidence: 96%

Biology and Biophysics of the Nuclear Pore Complex and Its Components

Lim

Ullman

Fahrenkrog

2008

International Review of Cell and Molecular Biology

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“…A heuristic understanding of selective transport posits that the negative ∆H following binding will lower the Gibbs free energy of transport for molecules that can bind to FG nups (Fig. 5A,B, right) (Rout et al 2003;Nielsen et al 2006). This heuristic view is the essence of the "virtual gating" mechanism (Rout et al 2003).…”

Section: Binding Can Overcome Barriers Tomentioning

confidence: 99%

“…A narrow margin of affinities for binding sites was found that can enable selective yet rapid transport. It is thought that the affinity has to be sufficiently strong for selection but weak enough not to clog the pores (Macara 2001;Nielsen et al 2006;Zilman et al 2007). Transport channels coated with hairpin DNA have been shown to transport the complimentary oligos with singlebase mismatch selectivity (Kohli et al 2004).…”

Section: Channels Lined With Binding Sites Have Been Shown To Mediatementioning

confidence: 99%

“…In addition, the spatial distribution of binding sites along a channel only weakly affected rate of transport through the channel in a mathematical model (Zilman et al 2007). It has also been proposed that both the entrance and exit of the pore must contain binding sites for rapid selective transport to occur, because if there are no binding sites at one end, the entropic barrier at that end will impede transport (Nielsen et al 2006).…”

Section: Connecting Npc Structure With Transport Mechanismmentioning

confidence: 99%

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The Mechanism of Nucleocytoplasmic Transport through the Nuclear Pore Complex

Tetenbaum-Novatt

Rout²

2010

Cold Spring Harbor Symposia on Quantitative Biology

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The nuclear pore complex (NPC) mediates all transport between the nucleus and cytoplasm. Passage through the NPC is highly selective, yet the same channel must allow rapid specific transport of a wide range of cargoes. This chapter focuses mainly on the phenylalanine-glycine (FG) nucleoporins (nups), proteins carrying natively unfolded regions that are thought to form the selectively permeable barrier within the NPC. The physical properties of the FG nup barrier remain unclear. The high selectivity and rapidity of transport observed in vivo may be explained, in part, by competition for binding and space between transport factors and nontransported proteins. Future studies of FG nups will therefore also examine their interactions between FG nups and other proteins in their surroundings.

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“…The Wang-Landau technique allows us to give numerical estimates of the free energy under various system conditions. Although the WangLandau technique is still under development, it has been applied successfully for a range of problems, e.g., discrete lattice models [21], polymer properties [22], protein conformations [23] and the calculation of reaction rates [24]. In context of triangulated surfaces Wang-Landau algorithms have been used to obtain the genus-dependence of the density of states [25] and the specific heat of fixed connectivity surfaces [26].…”

Section: Introductionmentioning

confidence: 99%

The tension of framed membranes from computer simulations

2018

Self Cite

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Abstract.We have analyzed the behavior of a randomly triangulated, self-avoiding surface model of a flexible, fluid membrane subject to a circular boundary by Wang-Landau Monte Carlo computer simulation techniques. The dependence of the canonical free energy and frame tension on the frame area is obtained for flexible membranes. It is shown that for low bending rigidities the framed membrane is only stable above a threshold tension, suggesting a discontinuous transition from the collapsed (branched polymer) state to a finite tension extended state. In a tension range above this threshold tension the membranes display power-law characteristics for the equation of state, while higher tension levels includes both an extended linear (elastic) as well as a highly non-linear stretching regime. For semi-flexible membranes a transition from extended to buckled conformations takes place at negative frame tensions. Our analysis indicates that at zero frame tension the crumpling transition of fluid membranes show characteristics of both critical behavior and a discontinuous transition at low bending rigidities.

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Managing Free-energy Barriers in Nuclear Pore Transport

Cited by 10 publications

References 27 publications

Biology and Biophysics of the Nuclear Pore Complex and Its Components

Biology and Biophysics of the Nuclear Pore Complex and Its Components

The Mechanism of Nucleocytoplasmic Transport through the Nuclear Pore Complex

The tension of framed membranes from computer simulations

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