Article
Oncology
Bartlomiej Gielniewski, Katarzyna Poleszak, Adria-Jaume Roura, Paulina Szadkowska, Karol Jacek, Sylwia K. Krol, Rafal Guzik, Paulina Wiechecka, Marta Maleszewska, Beata Kaza, Andrzej Marchel, Tomasz Czernicki, Andrzej Koziarski, Grzegorz Zielinski, Andrzej Styk, Maciej Kawecki, Cezary Szczylik, Ryszard Czepko, Mariusz Banach, Wojciech Kaspera, Wojciech Szopa, Mateusz Bujko, Bartosz Czapski, Miroslaw Zabek, Ewa Izycka-Swieszewska, Wojciech Kloc, Pawel Nauman, Joanna Cieslewicz, Wieslawa Grajkowska, Natalia Morosini, Houtan Noushmehr, Bartosz Wojtas, Bozena Kaminska
Summary: High-grade gliomas are aggressive and deadly brain tumors with poor prognosis. In this study, genomic alterations and transcriptomic patterns in high-grade gliomas were analyzed. A recurrent mutation in the TOP2A gene was found in four GBMs, leading to altered DNA binding and relaxation activities. GBM patients carrying this mutation had shorter overall survival and transcriptomic alterations consistent with splicing dysregulation, suggesting its contribution to disease pathology.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Cell Biology
Eleni Petsalaki, Sofia Balafouti, Athina A. Kyriazi, George Zachos
Summary: The mechanism of how human cells sense chromatin bridges to delay completion of cytokinesis (abscission) is unknown. Petsalaki et al. found that Topoisomerase IIα-DNA covalent complexes are formed on knotted DNA and promote recruitment of downstream factors to chromatin bridges to activate the abscission checkpoint and prevent chromatin breakage. This study reveals the first mechanism by which the abscission checkpoint detects chromatin bridges, through generation of abortive Topoisomerase IIα-DNA cleavage complexes (Top2ccs) on DNA knots, to preserve genome integrity.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Julia A. M. Bakx, Andreas S. Biebricher, Graeme A. King, Panagiotis Christodoulis, Kata Sarlos, Anna H. Bizard, Ian D. Hickson, Gijs J. L. Wuite, Erwin J. G. Peterman
Summary: Topoisomerase IIIa is a type 1A topoisomerase that forms a complex with RMI1 and RMI2 called TRR in human cells. In this study, the authors used optical tweezers and fluorescence microscopy to investigate the catalytic steps of TRR. They found that TRR forms an open gate in single-stranded DNA and can bind a second single-stranded or double-stranded DNA molecule, leading to catenation. Interestingly, double-stranded DNA binding increases the gate size and the helicase BLM affects the flexibility of the gate. These findings suggest that TRR-mediated transfer of double-stranded DNA may be more important than previously believed.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Shanti Pal Gangwar, Laura Y. Yen, Maria V. Yelshanskaya, Alexander I. Sobolevsky
Summary: In this study, cryo-EM structures of KAR GluK2 in complex with positive allosteric modulator BPAM344, competitive antagonist DNQX, and negative allosteric modulator perampanel were presented. The structures revealed the binding of two BPAM344 molecules per ligand-binding domain dimer interface. In the absence of an agonist or in the presence of DNQX, BPAM344 stabilized GluK2 in the closed state. The closed state was also stabilized by perampanel, which bound to the ion channel extracellular collar sites located in two out of four GluK2 subunits. These findings provide insights into the molecular mechanisms of positive and negative allosteric modulation of KARs.
Article
Biochemistry & Molecular Biology
Richard M. Walsh Jr, Shaun Rawson, Helena M. Schnell, Benjamin Velez, Tamayanthi Rajakumar, John Hanna
Summary: The assembly of the proteasome's core particle involves the collaboration of chaperones and subunit propeptides. Through cryogenic electron microscopy, this study reveals the structure of a post-fusion assembly intermediate of the proteasome, clarifying the role of associated factors in CP assembly and maturation.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Richard M. Walsh, Shaun Rawson, Helena M. Schnell, Benjamin Velez, Tamayanthi Rajakumar, John Hanna
Summary: The assembly of the proteasome's core particle (CP) requires chaperones and subunit propeptides. The study reveals the structural changes induced by midline-spanning interactions and the role of chaperones in the maturation process. The results suggest that cleavage may not be sufficient for propeptide release and propose a scaffolding role for chaperones in CP fusion and activation.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Inorganic & Nuclear
Jingtian Zhou, Qiudi Yue, Maksym Opanasenko, Xinyan Chen, Yajun Tao, Zhenlin Luo
Summary: This study investigated the disassembly and reassembly mechanism of three germanosilicate zeolites in HCl vapor, revealing three key steps and comparing their reaction behaviors.
INORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Engineering, Electrical & Electronic
B. Pathak, P. K. Kalita, Nayan Mani Nath, Ngangom Aomoa, J. P. Roy Choudhury
Summary: ZnO/PbO core/shell nanocomposites embedded in PVP matrix were prepared using a chemical method. The coating process increased the grain size and strain of the nanocomposites. Absorption studies showed blue shift and red shift effects, consistent with XRD results. The prepared core/shell nanocomposites exhibited excellent electrical properties and can be used as conductive devices.
MATERIALS SCIENCE IN SEMICONDUCTOR PROCESSING
(2022)
Article
Multidisciplinary Sciences
John T. Petroff, Noah M. Dietzen, Ezry Santiago-McRae, Brett Deng, Maya S. Washington, Lawrence J. Chen, K. Trent Moreland, Zengqin Deng, Michael Rau, James A. J. Fitzpatrick, Peng Yuan, Thomas T. Joseph, Jerome Henin, Grace Brannigan, Wayland W. L. Cheng
Summary: The model pLGIC ELIC is positively modulated by the anionic phospholipid phosphatidylglycerol, which stabilizes the activated, open-channel state of the pLGIC.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Vojtech Vyklicky, Cherise Stanley, Chris Habrian, Ehud Y. Isacoff
Summary: Activation of NMDARs involves closure of the ligand binding domains of GluN1 and GluN2 subunits, which are regulated allosterically by the ATD. Glutamate binding to GluN2 subunits elicits two identical, sequential steps of ATD dimer separation that are regulated by protons.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Eric Gibbs, Emily Klemm, David Seiferth, Arvind Kumar, Serban L. Ilca, Philip C. Biggin, Sudha Chakrapani
Summary: In this study, cryo-EM structures of the α1βGlyR in the presence of an antagonist, agonist, and agonist with a positive allosteric modulator were determined. The structures revealed distinct pore conformations with varying degrees of asymmetry, and the receptors were found to be in closed or desensitized states. Subunit-specific features and characteristics of the extracellular and intracellular domains were also identified. These findings provide a framework for further investigations into the function of this physiologically important channel.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Tuan A. Nguyen, Henry L. Puhl, Kirk Hines, Daniel J. Liput, Steven S. Vogel
Summary: The regulation and modulation of synaptic functions rely on a coordinated choreography of protein conformational changes and interactions, which are influenced by intracellular calcium dynamics. By using time-lapse Forster resonance energy transfer, we can study the dynamics of both conformational changes and protein-protein interactions simultaneously under physiological conditions.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Physical
Mohammad Taha, Sivacarendran Balendhran, Peter C. Sherrell, Nick Kirkwood, Dingchen Wen, Shifan Wang, Jiajun Meng, James Bullock, Kenneth B. Crozier, Len Sciacca
Summary: We have developed a method to lower the insulator-to-metal phase transition (IMT) temperature of vanadium oxide (VOx) to around 40 degrees Celsius, enabling near-room temperature infrared modulation. This approach involves controlling the metal oxide stoichiometry and using a SiO2 shell to induce strain in the VOx particles, effectively reducing the IMT temperature.
JOURNAL OF MATERIALS CHEMISTRY A
(2023)
Article
Biochemistry & Molecular Biology
Daniel N. Grba, James N. Blaza, Hannah R. Bridges, Ahmed-Noor A. Agip, Zhan Yin, Masatoshi Murai, Hideto Miyoshi, Judy Hirst
Summary: Mitochondrial complex I is a crucial enzyme in energy metabolism and plays a key role in ATP synthesis. This study reveals the structure of mouse complex I with a tight-binding acetogenin inhibitor, providing insights into the binding mode and structure-activity relationships. The amphipathic nature of the channel supports both tight binding of the inhibitor and rapid exchange of the substrate and product.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Cell Biology
Sayan Biswas
Summary: Cellular phenotypes are influenced by downstream targets of bioactive compound treatments, with computational methods used to identify subcellular targets and predict overall cellular responses. Diverse treatments display phenotypic diversity and varying effects on cellular integrity, indicating signaling heterogeneity. The study validates a prediction model against new compounds and reveals evidence of signaling plasticity in signaling cascades. Image-based profiling approaches offer insights for target identification in drug and disease states.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)
