Article
Biochemistry & Molecular Biology
Kathleen M. Lennon, Mohammad Soheilypour, Mohaddeseh Peyro, Devin L. Wakefield, Grace E. Choo, Mohammad R. K. Mofrad, Tijana Jovanovic-Talisman
Summary: This study investigates the mechanism of transport across the nuclear envelope via the nuclear pore complex by combining experimental and physical modeling approaches. By analyzing the composition of the NPC barrier and its interaction with nuclear transport receptors, the selectivity and regulation of transport were revealed. The results demonstrate that the binding of nuclear transport receptors is negatively cooperative and dependent on factors such as FG repeat number, fragment charge, and density.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biophysics
Luke K. Davis, Andela Saric, Bart W. Hoogenboom, Anton Zilman
Summary: Interactions between FG Nups and NTRs are crucial for cellular transport, with heterogeneity playing a significant role in binding and unbinding kinetics. Multivalency is a key factor influencing binding equilibria and kinetics. Single-molecule binding kinetics have little impact on NTR diffusion in polymer melts consisting of FG-Nup-like sequences.
BIOPHYSICAL JOURNAL
(2021)
Article
Multidisciplinary Sciences
Alessio Fragasso, Hendrik W. de Vries, John Andersson, Eli O. van der Sluis, Erik van der Giessen, Andreas Dahlin, Patrick R. Onck, Cees Dekker
Summary: This study successfully reconstituted the selective behavior of the NPC by introducing an artificial FG-Nup that mimics natural Nups, demonstrating that specific spacer sequences or spatial segregation of different FG-motif types are not needed to create selective NPCs.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Qi Shen, Taoran Tian, Qiancheng Xiong, Patrick D. Ellis Fisher, Yong Xiong, Thomas J. Melia, C. Patrick Lusk, Chenxiang Lin
Summary: Researchers have developed a biomimetic construct called NanoTrap using DNA nanotechnology to better understand how nucleoporins in the nuclear pore complex establish a selective barrier. The type of FG motif, grafting density, and spatial arrangement were found to be critical determinants of an effective diffusion barrier, with diffusion barriers formed with cohesive FG interactions dominating in mixed-FG-nup scenarios.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
ByeongJin Cho, Jaejun Choi, RyeongHyeon Kim, Jean Nyoung Yun, Yuri Choi, Hyung Ho Lee, Junseock Koh
Summary: The article presents basic thermodynamic models for the assembly of IDP hubs with multiple target proteins and advanced models to analyze the assembly of Nup153 hubs with multiple Kap molecules, revealing the complex organization of Kap binding sites and negative cooperativity. The study demonstrates the feasibility and potential mechanism for manifold regulation of IDP functions by diverse cellular signals.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Jiaojiao Wang, Gaofeng Pei, Yupei Wang, Dewei Wu, Xiaokang Liu, Gaoming Li, Jianfang He, Xiaolin Zhang, Xiaoyi Shan, Pilong Li, Daoxin Xie
Summary: This study revealed that the phase separation of the nuclear pore complex (NPC) central barrier plays a crucial role in regulating plant defense against various biotic stresses. The NUP62 gene was found to positively regulate plant defense against the plant pathogen Botrytis cinerea. Further investigation showed that the phase separation of the NPC central barrier regulates the nucleocytoplasmic transport of immune regulators and activates plant defense against a broad range of biotic stresses.
Article
Biochemistry & Molecular Biology
Yun Jung Yang, Danielle J. Mai, Shuaili Li, Melody A. Morris, Bradley D. Olsen
Summary: The study synthesized a nuclear pore-like protein by polymerizing the consensus repeat sequence of a yeast nucleoporin and explored the importance of positive net charge and alternating positive and negative charge within the hydrophilic spacer for recognition and selective transport. Mutations near and far from the interacting domain revealed the significance of spatial proximity of highly conserved residues in selective transport.
Article
Multidisciplinary Sciences
Bernhard Illes, Adrian Fuchs, Florian Gegenfurtner, Evelyn Ploetz, Stefan Zahler, Angelika M. Vollmar, Hanna Engelke
Summary: YAP activation may actively trigger invasion, as demonstrated through experiments using optoYAP. Activation of optoYAP induces invasion in cancer spheroids, suggesting that nuclear translocation may be sufficient to initiate invasion.
Article
Biochemistry & Molecular Biology
Wanlu Zhang, Azqa Khan, Jlenia Vitale, Annett Neuner, Kerstin Rink, Christian Luechtenborg, Britta Bruegger, Thomas H. Soellner, Elmar Schiebel
Summary: The short amphipathic alpha-helix of Apq12 regulates the function of Brl1 and Brr6, leading to defects in NPC biogenesis and NE integrity when disrupted. Overexpression of Apq12 promotes over-proliferation of the ONM/ER and accumulation of phosphatidic acid at the NE, possibly during NPC biogenesis.
Article
Biochemistry & Molecular Biology
Yuri Y. Shevelyov
Summary: Heterochromatin is mainly localized at the nuclear periphery by interacting with the nuclear lamina and nuclear pore complexes. Recent studies have shown that these interactions play a crucial role in maintaining its peripheral localization, and there are differences in chromatin interactions with the nuclear envelope in cell populations and individual cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Julie Jacquemyn, Joyce Foroozandeh, Katlijn Vints, Jef Swerts, Patrik Verstreken, Natalia Gounko, Sandra F. Gallego, Rose Goodchild
Summary: Torsin affects lipid metabolism by regulating NEP1R1-CTDNEP1 and Lipin, influencing nuclear envelope remodeling and nuclear pore complex biogenesis. This mechanism explains some of the pleiotropic effects of Torsins.
Article
Multidisciplinary Sciences
Ulrike Zinnall, Miha Milek, Igor Minia, Carlos H. Vieira-Vieira, Simon Mueller, Guido Mastrobuoni, Orsalia-Georgia Hazapis, Simone Del Giudice, David Schwefel, Nadine Bley, Franka Voigt, Jeffrey A. Chao, Stefan Kempa, Stefan Huettelmaier, Matthias Selbach, Markus Landthaler
Summary: HDLBP/Vigilin directly interacts with more than 80% of ER-localized mRNAs and plays an important role in the translation of ER-targeted mRNAs. Its absence leads to impaired protein synthesis and secretion, as well as decreased tumor growth.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Tiantian Zheng, Anton Zilman
Summary: The nuclear pore complexes (NPCs) in eukaryotic cells are responsible for macromolecular transport in and out of the nucleus. The NPCs contain intrinsically disordered proteins (IDPs) and efficiently transport cargoes in crowded conditions. A computational model of the NPC shows that self-regulating mechanisms and the spatial architecture of the IDP assembly contribute to efficient transport.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Physics, Multidisciplinary
P. Malgaretti, T. Nizkaia, G. Oshanin
Summary: In many practical problems, it is important to know the probability of reaching either end of a realistic corrugated channel before the other. These probabilities are called splitting probabilities (SPs) in mathematical literature. In this study, using the Fick-Jacobs approach, we analytically investigate the SPs as functions of system parameters for dynamics in three-dimensional corrugated channels, comparing standard diffusion and active Brownian motion. Our analysis reveals similarities and distinct features that can be attributed to the activity of particles.
Article
Chemistry, Multidisciplinary
Jose Arevalo-Fester, Alexander Briceno
Summary: Hydrophilic functionalized carbon nanotubes (MWCNT-COOH) were synthesized and their selective adsorption properties for cationic dyes were investigated. The results showed that MWCNT-raw could adsorb both anionic and cationic dyes, while MWCNT-COOH exhibited enhanced selectivity towards cationic dyes. Furthermore, the adsorbate-adsorbent interactions were dominated by hierarchical supramolecular interactions, which were influenced by surface modification, dye charge, temperature, and multivalent acceptor/donor capacity. Thermodynamic analysis revealed that the adsorption process on MWCNT-COOH was spontaneous and exothermic, with a reduction in entropy values due to the multivalent effect.
Article
Chemistry, Multidisciplinary
Adam J. Stevens, Giridhar Sekar, Josef A. Gramespacher, David Cowburn, Tom W. Muir
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2018)
Editorial Material
Multidisciplinary Sciences
Jennifer Cable, Clifford Brangwynne, Geraldine Seydoux, David Cowburn, Rohit V. Pappu, Carlos A. Castaneda, Luke E. Berchowitz, Zhijuan Chen, Martin Jonikas, Abby Dernburg, Tanja Mittag, Nicolas L. Fawzi
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2019)
Article
Oncology
Bhartesh A. Shah, Cheongeun Oh, S. Peter Wu, Jerome M. Karp, Michael Grossbard, Naamit K. Gerber
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2020)
Article
Operations Research & Management Science
Jose F. S. Bravo-Ferreira, David Cowburn, Yuehaw Khoo, Amit Singer
Summary: Nuclear Magnetic Resonance (NMR) Spectroscopy is a key technique for protein structure determination, with a challenge being the assignment of resonance frequencies to atoms. The introduction of LIAN, a novel linear programming formulation, has led to state-of-the-art results in simulated and experimental datasets.
JOURNAL OF GLOBAL OPTIMIZATION
(2022)
Article
Multidisciplinary Sciences
Updesh Dixit, Savita Bhutoria, Xuhong Wu, Liming Qiu, Menachem Spira, Sheeba Mathew, Richard Harris, Lucas J. Adams, Sean Cahill, Rajiv Pathak, P. Rajesh Kumar, Minh Nguyen, Seetharama A. Acharya, Michael Brenowitz, Steven C. Almo, Xiaoqin Zou, Alasdair C. Steven, David Cowburn, Mark Girvin, Ganjam Kalpana
Summary: INI1/SMARCB1 interacts with HIV-1 integrase (IN) through its Rpt1 domain and plays multiple roles in HIV-1 replication. Research shows that the residues at the interface of INI1-Rpt1/IN-CTD overlap with those required for IN/RNA interaction, indicating a common binding mechanism for INI1 and RNA. Additionally, computational modeling suggests structural mimicry between INI1-Rpt1 and TAR RNA in their interactions with IN-CTD.
NATURE COMMUNICATIONS
(2021)
Article
Otorhinolaryngology
Jerome M. Karp, Kenneth S. Hu, Michael Persky, Mark Persky, Adam Jacobson, Theresa Tran, Zujun Li, Babak Givi, Moses M. Tam
Summary: Sinonasal cancers often present as advanced diseases, and national guidelines recommend systemic therapy and radiotherapy for managing T4b tumors. Recent studies suggest that adding surgical resection may improve local control and survival rates. Analysis of the National Cancer Database showed that incorporating surgery in the treatment of T4b sinonasal squamous cell carcinoma was associated with promising survival outcomes.
OTOLARYNGOLOGY-HEAD AND NECK SURGERY
(2022)
Article
Microbiology
Ryan J. Malonis, George Georgiev, Denise Haslwanter, Laura A. VanBlargan, Georgia Fallon, Olivia Vergnolle, Sean M. Cahill, Richard Harris, David Cowburn, Kartik Chandran, Michael S. Diamond, Jonathan R. Lai
Summary: By creating a subunit-based nanoparticle immunogen, we were able to induce the production of neutralizing and protective antibodies against POWV infection in mice. Our study provides insights into the molecular determinants of antibody-mediated neutralization and protection against TBFVs.
Article
Cell Biology
Santiago Naranjo, Christina M. Cabana, Lindsay M. LaFave, Rodrigo Romero, Sean-Luc Shanahan, Arjun Bhutkar, Peter M. K. Westcott, Jason M. Schenkel, Arkopravo Ghosh, Laura Z. Liao, Isabella Del Priore, Dian Yang, Tyler Jacks
Summary: In this study, the authors describe optimized conditions for expanding murine alveolar type 2 cells in organoid culture. They used this system to develop immunocompetent organoid-based models of KRAS, BRAF, and ALK mutant LUAD, demonstrating its power and versatility in studying lung cancer.
GENES & DEVELOPMENT
(2022)
Article
Chemistry, Multidisciplinary
Giridhar Sekar, Adam J. Stevens, Anahita Z. Mostafavi, Pulikallu Sashi, Tom W. Muir, David Cowburn
Summary: Split intein-mediated protein trans-splicing (PTS) is a widely used method in chemical biology and biotechnology for traceless and specific protein ligation. The efficiency of PTS can be limited by external residues flanking the intein. In this study, a recently developed atypically split intein (Cat) was further modified to enhance its PTS activity in the presence of unfavorable N-extein residues. The mechanism behind the enhanced activity was explored using nuclear magnetic resonance spectroscopy and molecular dynamics simulations, highlighting the contribution of a conserved histidine residue. This enhanced extein tolerance of Cat* expands the applicability of atypically split inteins and reveals common principles of extein dependence.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Editorial Material
Oncology
Jerome M. Karp
PRACTICAL RADIATION ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
David Cowburn, Michael Rout
Summary: Nuclear pore complexes (NPCs) play a crucial role in material exchange between the nucleus and cytoplasm, with a specific focus on nucleic acids and proteins. While the static structure of NPCs has been well defined, the functional roles of certain dynamic components, such as phenylalanyl-glycyl (FG) repeat rich nucleoporins, remain unclear. However, advancements in technical approaches and modeling methods may soon provide a more accurate and detailed understanding of NPC transport, potentially at the atomic level. Such progress would be invaluable in comprehending the impact of malfunctioning NPCs in various diseases.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Biochemistry & Molecular Biology
George Georgiev, Ryan J. Malonis, Ariel S. Wirchnianski, Alex W. Wessel, Helen S. Jung, Sean M. Cahill, Elisabeth K. Nyakatura, Olivia Vergnolle, Kimberly A. Dowd, David Cowburn, Theodore C. Pierson, Michael S. Diamond, Jonathan R. Lai
Summary: Researchers have developed a recombinant ZIKV immunogen using protein engineering techniques, which can elicit a protective immune response with reduced potential for producing enhancing antibodies.
CELL CHEMICAL BIOLOGY
(2022)