scholarly journals Decision letter: Simple biophysics underpins collective conformations of the intrinsically disordered proteins of the Nuclear Pore Complex

2015 ◽  
Keyword(s):  
Nuclear Pore Complex ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Nuclear Pore ◽  
Intrinsically Disordered

scholarly journals A Study of Intrinsically Disordered Proteins from Nuclear Pore Complex

2013 ◽  
Vol 104 (2) ◽  
pp. 55a-56a
Author(s):  
Jianhui Tian ◽  
Anton Zilman ◽  
Sandrasegaram Gnanakaran
Keyword(s):  
Nuclear Pore Complex ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Nuclear Pore ◽  
Intrinsically Disordered

scholarly journals Physical modelling of multivalent interactions in the nuclear pore complex

2020 ◽  
Author(s):  
Luke K. Davis ◽  
Anđela Šarić ◽  
Bart W. Hoogenboom ◽  
Anton Zilman
Keyword(s):  
Experimental Data ◽  
Single Molecule ◽  
Nuclear Pore Complex ◽  
Intrinsically Disordered Proteins ◽  
Binding Kinetics ◽  
Disordered Proteins ◽  
Minor Role ◽  
Nuclear Pore ◽  
Minimal Models ◽  
Intrinsically Disordered

In the nuclear pore complex (NPC), intrinsically disordered proteins (FG Nups) along with their interactions with more globular proteins called nuclear transport receptors (NTRs) are vital to the selectivity of transport into and out of the cell nucleus. While such interactions can be modelled at different levels of coarse graining, in-vitro experimental data have been quantitatively described by minimal models that describe FG Nups as cohesive homogeneous polymers and NTRs as uniformly cohesive spheres, where the heterogeneous effects have been smeared out. By definition, these minimal models do not account for the explicit heterogeneities in FG Nup sequences, essentially a string of cohesive and non-cohesive polymer units, and at the NTR surface. Here, we develop computational and analytical models that do take into account such heterogeneity at a level of minimal complexity, and compare them to experimental data on single-molecule interactions between FG Nups and NTRs. Overall, we find that the heterogeneous nature of FG Nups and NTRs plays a minor role for their equilibrium binding properties, but is of significance when it comes to (un)binding kinetics. Using our models, we predict how binding equilibria and kinetics depend on the distribution of cohesive blocks in the FG Nup sequences and of the binding pockets at the NTR surface, with multivalency playing a key role. Finally, we observe that single-molecule binding kinetics has a rather minor influence on the diffusion of NTRs in polymer melts consisting of FG-Nup-like sequences.

scholarly journals Intrinsically Disordered Proteins: Gatekeepers of the Nuclear Pore Complex

2016 ◽  
Vol 110 (3) ◽  
pp. 358a
Author(s):  
Ali Ghavami ◽  
Liesbeth M. Veenhoff ◽  
Erik Van der Giessen ◽  
Patrick R. Onck
Keyword(s):  
Nuclear Pore Complex ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Nuclear Pore ◽  
Intrinsically Disordered

scholarly journals DNA origami scaffold for studying intrinsically disordered proteins of the nuclear pore complex

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Philip Ketterer ◽  
Adithya N. Ananth ◽  
Diederik S. Laman Trip ◽  
Ankur Mishra ◽  
Eva Bertosin ◽  
...  
Keyword(s):  
Nuclear Pore Complex ◽  
Intrinsically Disordered Proteins ◽  
Dna Origami ◽  
Disordered Proteins ◽  
Nuclear Pore ◽  
Intrinsically Disordered

scholarly journals Converging on the function of intrinsically disordered nucleoporins in the nuclear pore complex

2010 ◽  
Vol 391 (7) ◽  
Author(s):  
Orit Peleg ◽  
Roderick Y.H. Lim
Keyword(s):  
Nuclear Pore Complex ◽  
Intrinsically Disordered Proteins ◽  
Molecular Transport ◽  
Disordered Proteins ◽  
Nuclear Pore ◽  
Biological Mechanisms ◽  
Intrinsically Disordered ◽  
Polymeric Chains ◽  
Insight Into

Abstract Several biological mechanisms involve proteins or proteinaceous components that are intrinsically disordered. A case in point pertains to the nuclear pore complex (NPC), which regulates molecular transport between the nucleus and the cytoplasm. NPC functionality is dependent on unfolded domains rich in Phe-Gly (FG) repeats (i.e., FG-domains) that collectively act to promote or hinder cargo translocation. To a large extent, our understanding of FG-domain behavior is limited to in vitro investigations given the difficulty to resolve them directly in the NPC. Nevertheless, recent findings indicate a collective convergence towards rationalizing FG-domain function. This review aims to glean further insight into this fascinating problem by taking an objective look at the boundary conditions and contextual details underpinning FG-domain behavior in the NPC. Here, we treat the FG-domains as being commensurate with polymeric chains to address ambiguities such as for instance, how FG-domains tethered to the central channel of the NPC would behave differently as compared with their free-floating counterparts in solution. By bringing such fundamental questions to the fore, this review seeks to illuminate the importance of how such parameters can hold influence over the structure-function relation of intrinsically disordered proteins in the NPC and beyond.

scholarly journals Simple biophysics underpins collective conformations of the intrinsically disordered proteins of the Nuclear Pore Complex

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Andrei Vovk ◽  
Chad Gu ◽  
Michael G Opferman ◽  
Larisa E Kapinos ◽  
Roderick YH Lim ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Intrinsically Disordered Proteins ◽  
Nucleocytoplasmic Transport ◽  
Transport Proteins ◽  
Disordered Proteins ◽  
Biophysical Model ◽  
Nuclear Pore ◽  
Intrinsically Disordered

Nuclear Pore Complexes (NPCs) are key cellular transporter that control nucleocytoplasmic transport in eukaryotic cells, but its transport mechanism is still not understood. The centerpiece of NPC transport is the assembly of intrinsically disordered polypeptides, known as FG nucleoporins, lining its passageway. Their conformations and collective dynamics during transport are difficult to assess in vivo. In vitro investigations provide partially conflicting results, lending support to different models of transport, which invoke various conformational transitions of the FG nucleoporins induced by the cargo-carrying transport proteins. We show that the spatial organization of FG nucleoporin assemblies with the transport proteins can be understood within a first principles biophysical model with a minimal number of key physical variables, such as the average protein interaction strengths and spatial densities. These results address some of the outstanding controversies and suggest how molecularly divergent NPCs in different species can perform essentially the same function.

scholarly journals The molecular mechanism of nuclear transport revealed by atomic-scale measurements

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Loren E Hough ◽  
Kaushik Dutta ◽  
Samuel Sparks ◽  
Deniz B Temel ◽  
Alia Kamal ◽  
...  
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Atomic Scale ◽  
Disordered Proteins ◽  
Nuclear Pore ◽  
Resonance Spectroscopy ◽  
Nuclear Pore Complexes ◽  
Selective Filter ◽  
Intrinsically Disordered ◽  
Cellular Environment ◽  
Pore Complexes

Nuclear pore complexes (NPCs) form a selective filter that allows the rapid passage of transport factors (TFs) and their cargoes across the nuclear envelope, while blocking the passage of other macromolecules. Intrinsically disordered proteins (IDPs) containing phenylalanyl-glycyl (FG)-rich repeats line the pore and interact with TFs. However, the reason that transport can be both fast and specific remains undetermined, through lack of atomic-scale information on the behavior of FGs and their interaction with TFs. We used nuclear magnetic resonance spectroscopy to address these issues. We show that FG repeats are highly dynamic IDPs, stabilized by the cellular environment. Fast transport of TFs is supported because the rapid motion of FG motifs allows them to exchange on and off TFs extremely quickly through transient interactions. Because TFs uniquely carry multiple pockets for FG repeats, only they can form the many frequent interactions needed for specific passage between FG repeats to cross the NPC.

scholarly journals The Effect of FG-Nup Phosphorylation on NPC Selectivity: A One-Bead-Per-Amino-Acid Molecular Dynamics Study

2019 ◽  
Vol 20 (3) ◽  
pp. 596 ◽  
Author(s):  
Ankur Mishra ◽  
Wouter Sipma ◽  
Liesbeth Veenhoff ◽  
Erik Van der Giessen ◽  
Patrick Onck
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Intrinsically Disordered Proteins ◽  
Protein Complexes ◽  
Disordered Proteins ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Intrinsically Disordered ◽  
Dynamics Simulations ◽  
Pore Complexes

Nuclear pore complexes (NPCs) are large protein complexes embedded in the nuclear envelope separating the cytoplasm from the nucleoplasm in eukaryotic cells. They function as selective gates for the transport of molecules in and out of the nucleus. The inner wall of the NPC is coated with intrinsically disordered proteins rich in phenylalanine-glycine repeats (FG-repeats), which are responsible for the intriguing selectivity of NPCs. The phosphorylation state of the FG-Nups is controlled by kinases and phosphatases. In the current study, we extended our one-bead-per-amino-acid (1BPA) model for intrinsically disordered proteins to account for phosphorylation. With this, we performed molecular dynamics simulations to probe the effect of phosphorylation on the Stokes radius of isolated FG-Nups, and on the structure and transport properties of the NPC. Our results indicate that phosphorylation causes a reduced attraction between the residues, leading to an extension of the FG-Nups and the formation of a significantly less dense FG-network inside the NPC. Furthermore, our simulations show that upon phosphorylation, the transport rate of inert molecules increases, while that of nuclear transport receptors decreases, which can be rationalized in terms of modified hydrophobic, electrostatic, and steric interactions. Altogether, our models provide a molecular framework to explain how extensive phosphorylation of FG-Nups decreases the selectivity of the NPC.

scholarly journals New Family Members of FG Repeat Proteins and Their Unexplored Roles During Phase Separation

2021 ◽  
Vol 9 ◽  
Author(s):  
Yoichi Shinkai ◽  
Masahiro Kuramochi ◽  
Takamitsu Miyafusa
Keyword(s):  
Phase Separation ◽  
Intrinsically Disordered Proteins ◽  
Biological Function ◽  
Disordered Proteins ◽  
Nuclear Pore ◽  
Intrinsically Disordered ◽  
New Family ◽  
Repeat Proteins ◽  
Barrier Formation ◽  
Repeat Domain

The condensation and compartmentalization of biomacromolecules in the cell are driven by the process of phase separation. The main effectors of phase separation are intrinsically disordered proteins, which include proteins with a phenylalanine-glycine (FG) repeat domain. Our understanding of the biological function of FG repeat proteins during phase separation has been mainly derived from recent research on a member of the nuclear pore complex proteins, nucleoporins containing FG repeat domain (FG-NUPs). FG-NUPs form meshwork structures by inter- and intra-molecular FG domain interactions, which confine the nucleo-cytoplasmic exchange. Whereas FG-NUPs localize in the nuclear membrane, other FG repeat proteins reside in the cytoplasm and the nucleoplasm, and the biological function of the FG repeat domain of these proteins is not well described. In the present review, we list the FG repeat proteins that are known to phase separate in the cell, and review their biological functions. We extract the unraveled features of FG repeat proteins as an activator of barrier formation and homotypic cell-cell interactions. Understanding the regulatory mechanisms of FG repeat proteins will provide a potential delivery tool for therapeutic reagents.

Sign in / Sign up

Export Citation Format

Share Document