Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Probing a structural model of the nuclear pore complex channel through molecular dynamics.

ABSTRACT: The central pore of a nuclear pore complex (NPC) is filled with unstructured proteins that contain many FG-repeats separated by hydrophilic regions. An example of such protein is nsp1. By simulating an array of nsp1 segments, we identified, in an earlier study, a spontaneously formed brushlike structure that promises to explain selective transport in the NPC channel. Here we report four (350,000 atom, 200 ns) simulations probing this structure via its interaction with transport receptor NTF2 as well as with an inert protein. NTF2 dimers are observed to gradually enter the brush, but the inert protein is not. Both NTF2 and the inert protein are found to bind to FG-repeats, but binding periods lasted more briefly for the inert protein. A simulation also investigated the behavior of a brush made of mutant nsp1 that is known to be less effective in NPC-selective transport, finding that this brush does not attract NTF2.

SUBMITTER: Miao L

PROVIDER: S-EPMC2865169 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Probing a structural model of the nuclear pore complex channel through molecular dynamics.

Miao Lingling L Schulten Klaus K

Biophysical journal 20100401 8

The central pore of a nuclear pore complex (NPC) is filled with unstructured proteins that contain many FG-repeats separated by hydrophilic regions. An example of such protein is nsp1. By simulating an array of nsp1 segments, we identified, in an earlier study, a spontaneously formed brushlike structure that promises to explain selective transport in the NPC channel. Here we report four (350,000 atom, 200 ns) simulations probing this structure via its interaction with transport receptor NTF2 as ...[more]

PMID: 20409487

Similar Datasets

Probing the disordered domain of the nuclear pore complex through coarse-grained molecular dynamics simulations.

Project description:The distribution of disordered proteins (FG-nups) that line the transport channel of the nuclear pore complex (NPC) is investigated by means of coarse-grained molecular dynamics simulations. A one-bead-per-amino-acid model is presented that accounts for the hydrophobic/hydrophilic and electrostatic interactions between different amino acids, polarity of the solvent, and screening of free ions. The results indicate that the interaction of the FG-nups forms a high-density, doughnut-like distribution inside the NPC, which is rich in FG-repeats. We show that the obtained distribution is encoded in the amino-acid sequence of the FG-nups and is driven by both electrostatic and hydrophobic interactions. To explore the relation between structure and function, we have systematically removed different combinations of FG-nups from the pore to simulate inviable and viable NPCs that were previously studied experimentally. The obtained density distributions show that the maximum density of the FG-nups inside the pore does not exceed 185 mg/mL in the inviable NPCs, whereas for the wild-type and viable NPCs, this value increases to 300 mg/mL. Interestingly, this maximum density is not correlated to the total mass of the FG-nups, but depends sensitively on the specific combination of essential Nups located in the central plane of the NPC.

| S-EPMC4167297 | biostudies-literature

Molecular and structural analysis of central transport channel in complex with Nup93 of nuclear pore complex.

Project description:The central transport channel (CTC) of nuclear pore complexes (NPCs) is made up of three nucleoporins Nup62, Nup58 and Nup54. In which manner and capacity, these nucleoporins form the CTC, is not yet clear. We explored the CTC Nups from various species and observed that distinct biochemical characteristics of CTC Nups are evolutionarily conserved. Moreover, comparative biochemical analysis of CTC complexes showed various stoichiometric combinations of Nup62, Nup54 and Nup58 coexisting together. We observed the conserved amino-terminal domain of mammalian Nup93 is crucial for the anchorage of CTC and its localization to NPCs. We could reconstitute and purify mammalian CTC·Nup93 quaternary complex by co-expressing full length or N-terminal domain of Nup93 along with CTC complex. Further, we characterized CTC·Nup93 complex using small angle X-ray scattering and electron microscopy that revealed a "V" shape of CTC·Nup93 complex. Overall, this study demonstrated for the first time evolutionarily conserved plasticity and stoichiometric diversity in CTC Nups.

| S-EPMC7679962 | biostudies-literature

Dissecting the Structural Dynamics of the Nuclear Pore Complex.

Project description:Cellular processes are largely carried out by macromolecular assemblies, most of which are dynamic, having components that are in constant flux. One such assembly is the nuclear pore complex (NPC), an ∼50 MDa assembly comprised of ∼30 different proteins called Nups that mediates selective macromolecular transport between the nucleus and cytoplasm. We developed a proteomics method to provide a comprehensive picture of the yeast NPC component dynamics. We discovered that, although all Nups display uniformly slow turnover, their exchange rates vary considerably. Surprisingly, this exchange rate was relatively unrelated to each Nup's position, accessibility, or role in transport but correlated with its structural role; scaffold-forming Nups exchange slowly, whereas flexible connector Nups threading throughout the NPC architecture exchange more rapidly. Targeted perturbations in the NPC structure revealed a dynamic resilience to damage. Our approach opens a new window into macromolecular assembly dynamics.

| S-EPMC8121378 | biostudies-literature

Project description:Nuclear pore complexes (NPCs) are selectively gated pathways between nucleoplasm and cytoplasm. Whereas small molecules can diffuse freely through NPCs, large molecules (>40 kD) can pass only when bound to transport receptors. The NPC central channel is filled with disordered proteins, rich in phenylalanine-glycine (FG) repeats, referred to as FG-nups. Our simulations, carried out at coarse-grained and all-atom levels, show that arrays of FG-nups tethered to a planar surface, at an FG-repeat density found in the NPC, form dynamic brush-like structures of multiprotein bundles, whereas individual FG-nups form dynamic globular structures. More than half of the FG-repeats are found on the surface of the bundles, offering a favorable environment for transport receptors. Binding to FG-repeats and a sliding motion of NTF2 induced by binding and unbinding to phenylalanines were observed when adding this transport receptor into one of the brush-like structures.

| S-EPMC2701619 | biostudies-literature

Molecular architecture of the transport channel of the nuclear pore complex.

Project description:The nuclear pore complex encloses a central channel for nucleocytoplasmic transport, which is thought to consist of three nucleoporins, Nup54, Nup58, and Nup62. However, the structure and composition of the channel are elusive. We determined the crystal structures of the interacting domains between these nucleoporins and pieced together the molecular architecture of the mammalian transport channel. Located in the channel midplane is a flexible Nup54?Nup58 ring that can undergo large rearrangements yielding diameter changes from ?20 to ?40 nm. Nup62?Nup54 triple helices project alternately up and down from either side of the midplane ring and form nucleoplasmic and cytoplasmic entries. The channel consists of as many as 224 copies of the three nucleoporins, amounting to a molar mass of 12.3 MDa and contributing 256 phenylalanine-glycine repeat regions. We propose that the occupancy of these repeat regions with transport receptors modulates ring diameter and transport activity.

| S-EPMC3431207 | biostudies-literature

Probing nuclear pore complex architecture with proximity-dependent biotinylation.

Project description:Proximity-dependent biotin identification (BioID) is a method for identifying protein associations that occur in vivo. By fusing a promiscuous biotin ligase to a protein of interest expressed in living cells, BioID permits the labeling of proximate proteins during a defined labeling period. In this study we used BioID to study the human nuclear pore complex (NPC), one of the largest macromolecular assemblies in eukaryotes. Anchored within the nuclear envelope, NPCs mediate the nucleocytoplasmic trafficking of numerous cellular components. We applied BioID to constituents of the Nup107-160 complex and the Nup93 complex, two conserved NPC subcomplexes. A strikingly different set of NPC constituents was detected depending on the position of these BioID-fusion proteins within the NPC. By applying BioID to several constituents located throughout the extremely stable Nup107-160 subcomplex, we refined our understanding of this highly conserved subcomplex, in part by demonstrating a direct interaction of Nup43 with Nup85. Furthermore, by using the extremely stable Nup107-160 structure as a molecular ruler, we defined the practical labeling radius of BioID. These studies further our understanding of human NPC organization and demonstrate that BioID is a valuable tool for exploring the constituency and organization of large protein assemblies in living cells.

| S-EPMC4066523 | biostudies-literature

Probing the nucleoporin FG repeat network defines structural and functional features of the nuclear pore complex.

Project description:Unraveling the organization of the FG repeat meshwork that forms the active transport channel of the nuclear pore complex (NPC) is key to understanding the mechanism of nucleocytoplasmic transport. In this paper, we develop a tool to probe the FG repeat network in living cells by modifying FG nucleoporins (Nups) with a binding motif (engineered dynein light chain-interacting domain) that can drag several copies of an interfering protein, Dyn2, into the FG network to plug the pore and stop nucleocytoplasmic transport. Our method allows us to specifically probe FG Nups in vivo, which provides insight into the organization and function of the NPC transport channel.

| S-EPMC3198172 | biostudies-literature

An agent-based model for mRNA export through the nuclear pore complex.

Project description:mRNA export from the nucleus is an essential step in the expression of every protein- coding gene in eukaryotes, but many aspects of this process remain poorly understood. The density of export receptors that must bind an mRNA to ensure export, as well as how receptor distribution affects transport dynamics, is not known. It is also unclear whether the rate-limiting step for transport occurs at the nuclear basket, in the central channel, or on the cytoplasmic face of the nuclear pore complex. Using previously published biophysical and biochemical parameters of mRNA export, we implemented a three-dimensional, coarse-grained, agent-based model of mRNA export in the nanosecond regime to gain insight into these issues. On running the model, we observed that mRNA export is sensitive to the number and distribution of transport receptors coating the mRNA and that there is a rate-limiting step in the nuclear basket that is potentially associated with the mRNA reconfiguring itself to thread into the central channel. Of note, our results also suggest that using a single location-monitoring mRNA label may be insufficient to correctly capture the time regime of mRNA threading through the pore and subsequent transport. This has implications for future experimental design to study mRNA transport dynamics.

| S-EPMC4230623 | biostudies-literature

Channel Nuclear Pore Complex subunits are required for transposon silencing in Drosophila

Project description:We investigate the transcription and export of the uni-strand piRNA cluster flamenco and report the involvement of Nuclear Pore Complex subunits in its nuclear export and specification as a piRNA precursor.

2021-04-15 | GSE152297 | GEO

Energetics of Transport through the Nuclear Pore Complex.

Project description: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.

| S-EPMC4764519 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data