scholarly journals Multifunctionality of F-rich nucleoporins

2020 ◽  
Vol 48 (6) ◽  
pp. 2603-2614
Author(s):  
Nike Heinß ◽  
Mikhail Sushkin ◽  
Miao Yu ◽  
Edward A. Lemke
Keyword(s):  
High Speed ◽  
Intrinsically Disordered Proteins ◽  
Nucleocytoplasmic Transport ◽  
Disordered Proteins ◽  
Nuclear Pore ◽  
Permeability Barrier ◽  
Biological Processes ◽  
Macromolecular Assembly ◽  
Intrinsically Disordered ◽  
The Family

Nucleoporins (Nups) represent a range of proteins most known for composing the macromolecular assembly of the nuclear pore complex (NPC). Among them, the family of intrinsically disordered proteins (IDPs) phenylalanine-glycine (FG) rich Nups, form the permeability barrier and coordinate the high-speed nucleocytoplasmic transport in a selective way. Those FG-Nups have been demonstrated to participate in various biological processes besides nucleocytoplasmic transport. The high number of accessible hydrophobic motifs of FG-Nups potentially gives rise to this multifunctionality, enabling them to form unique microenvironments. In this review, we discuss the multifunctionality of disordered and F-rich Nups and the diversity of their localizations, emphasizing the important roles of those Nups in various regulatory and metabolic processes.

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 chaperone DNAJB6 provides surveillance of FG-Nups and is required for interphase nuclear pore complex biogenesis

2021 ◽  
Author(s):  
E. F. Elsiena Kuiper ◽  
Paola Gallardo ◽  
Tessa Bergsma ◽  
Muriel Mari ◽  
Maiara Kolbe Musskopf ◽  
...  
Keyword(s):  
Molecular Chaperone ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Nuclear Pore ◽  
Permeability Barrier ◽  
Nuclear Pore Complexes ◽  
Annulate Lamellae ◽  
Intrinsically Disordered ◽  
Pore Complexes

Biogenesis of nuclear pore complexes (NPCs) includes the formation of the permeability barrier composed of phenylalanine-glycine-rich nucleoporins (FG-Nups) that regulate the selective passage/crossing of biomolecules. The FG-Nups are intrinsically disordered and prone to liquid-liquid phase separate and aggregate when isolated. It has remained largely unclear how FG-Nups are protected from making inappropriate interactions during NPC biogenesis. We found that DNAJB6, a molecular chaperone of the heat shock protein network, formed foci next to NPCs. The number of these foci decreases upon removal of proteins involved in the early steps of interphase NPC biogenesis. Reversely, when this process is stalled in the last steps, the number of DNAJB6-containing foci increases and they could be identified as herniations at the nuclear envelope (NE). Immunoelectron tomography showed that DNAJB6 localizes inside the lumen of the herniations arising at NPC biogenesis intermediates. Interestingly, loss of DNAJB6 results in annulate lamellae, which are structures containing partly assembled NPCs associated with disturbances in NPC biogenesis. We find that DNAJB6 binds to FG-Nups and can prevent the aggregation of the FG-region of several FG-Nups in cells and in vitro. Together, our data show that DNAJB6 provides quality control during NPC biogenesis and is the first molecular chaperone that is involved in the surveillance of native intrinsically disordered proteins, including FG-Nups.

scholarly journals Intrinsically Disordered Proteins as Regulators of Transient Biological Processes and as Untapped Drug Targets

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2118
Author(s):  
Yusuke Hosoya ◽  
Junko Ohkanda
Keyword(s):  
Drug Targets ◽  
Intrinsically Disordered Proteins ◽  
Dynamic Control ◽  
Disordered Proteins ◽  
Biological Processes ◽  
Phase Separations ◽  
Cellular Processes ◽  
Intrinsically Disordered ◽  
New Drug ◽  
Liquid Phase Separations

Intrinsically disordered proteins (IDPs) are critical players in the dynamic control of diverse cellular processes, and provide potential new drug targets because their dysregulation is closely related to many diseases. This review focuses on several medicinal studies that have identified low-molecular-weight inhibitors of IDPs. In addition, clinically relevant liquid–liquid phase separations—which critically involve both intermolecular interactions between IDPs and their posttranslational modification—are analyzed to understand the potential of IDPs as new drug targets.

Topological frustration leading to backtracking in a coupled folding-binding process

2021 ◽  
Author(s):  
Meng Gao ◽  
Ping Li ◽  
Zhengding Su ◽  
Yongqi Huang
Keyword(s):  
Structure Function ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Biological Processes ◽  
Sequence Structure ◽  
Binding Process ◽  
Intrinsically Disordered

Intrinsically disordered proteins (IDPs) are abundant in all species. Their discovery challenges the traditional “sequence−structure−function” paradigm of protein science, because IDPs play important roles in various biological processes without preformed...

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 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
Sign in / Sign up

Export Citation Format

Share Document